First Generation

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George Alexander WHEELER Dr.

1. George Alexander WHEELER Dr.1 Born on 10 Mar 1885 in Hog Branch Higgins  Yancey Co NC. George Alexander died in Spartanburg, SC, on 24 Dec 1981; he was 96. Spartanburg SC. Buried in Greenlawn Memorial Gardens. Spartanburg SC. Occupation: Doctor. George Alexander married Agnes Elizabeth Kullgran. Born in Conn.

S.C. Doctor Recalls Pellagra Controversy - By Kent Krell, Associated Press Writer - SPARTANBURG, S.C. (AP) - Dr. George A. Wheeler lives in quiet retirement near Spartanburg where half a century ago he was a central figure in an international medical controversy. In 1914, Dr. Wheeler, then a young medical school graduate, joined forces with Dr. Joseph Goldberger of the U.S. Public Health Service to prove that the dreaded pellagra was a dietary deficiency and not a contagious disease. Pellagra was peculiar to sections of Southeastern United States and parts of Italy where food staples - such as corn and maise - were lacking in necessary food protein. Pellagra was particularly prevalent among low income families in textile communities. Symptoms were a sore tongue and rash on the hands. The disease often evolved into severe mental disorders, leading in some cases to death.  Dr. Wheeler has vivid memories of those “hard times” when the prevailing medical opinions held that pellagra was a communicable disease. Drs. Wheeler and Goldberger set up a 45-bed hospital at Spartanburg in 1914 with the intention of proving their theories. The hospital had a waiting list of 500 patients at the outset, but by 1922 it closed for lack of patients.  By 1914, recalls Dr. Wheeler, the incidence of pellagra had reached the point “where ambulant pellagra patients were frequently seen along the streets. A key experiment at the Spartanburg Pellagra Hospital, says Dr. Wheeler was one in which fresh blood and other materials from pellagra patients was transmitted to healthy volunteers with uniformly negative results. Other experiments were carried out at orphanages and custodial institutions in the South. One was Epworth Orphanage in Columbia. At one orphanage the children were divided into three age groups and fed specific foods. Those under six got milk regularly and remained healthy. Those between 13 and 30 worked on the orphanage farm and avoided pellagra by eating vegetables. Pellagra cases developed in the six to 12 age bracket. These children subsisted mainly on grits, gravy, biscuits, molasses and poor quality fatback known as sowbelly. These were staple foods which filled the stomach, were cheap and easily stored. Drs. Goldberger and Wheeler arranged with authorities at Epworth and two orphanages in Mississippi to include in the diet certain supplemental items, such as lean meat and milk. Within a few months, pale, listless children got back their health.

Wheeler And Associates Proved to Everyone That Adjusted Diets Could Defeat Pellagra By Lee Oxenrider Staff Writer - Dr. George H. Wheeler of E. Main Street Extension in Spartanburg is a 91-year-old veteran of world famous adventure and exploration. He and associates were responsible for administering a knockout blow to what once was one of man’s most dread ailments -- pellagra. Here’s how it happened: Wheeler went to work for the U.S. Public Health Service in 1914. He was assigned to the team of Dr. Joseph Goldberger in the search for a cure for pellagra, which had become the number one killer in many areas of the South. “We went to orphanages, state institutions, prisons and poverty areas, where the disease seemed to be most prevalent,” Wheeler said this week. “It seemed to strike the poor and the institutionalized for some reason.” Goldberger and Wheeler thought a lot about the selectivity of pellagra, finally coming up with a theory contrary to the feelings of most physicians at that time. They decided that pellagra was not communicable . . . it was not “catching.” The final confirmation of their theory occurred in Spartanburg in 1916 when pellagra had reached epidemic proportions in many of the upstate mill villages. “We opened a pellagra hospital here with 45 beds; there was a waiting list of 500,” Wheeler recalled. “Five years later we couldn’t find any patients for our hospital. They had all been cured.” Many of the people who found the red rash on their knuckles and their necks, pain in their bowels and bones, had been living on a diet of cornmeal mush, grits, cane syrup, sow belly, very little fresh meat or milk. While most doctors were blaming the spread of the disease on sanitation problems, Goldberger and Wheeler adjusted diets in an effort to chase away the killer of so many of the Southern poor. They became convinced of their theory after they had arranged for the federal government to supplement the menu at the South Carolina and Georgia state mental institutions with fresh meat and milk. They found that orphans between 6 and 12 years of age were falling to pellagra. The younger children got fresh milk because the institutions felt that little children had to have it. The older children got it because they worked on the institution farms and took it for themselves at every opportunity. The in-between kids did chores around the orphanage and were given neither milk nor meat for the opportunity to steal it. They got, instead, a rash. The year after the research team altered the dietary program at two orphanages in Mississippi, 1,535 people died of pellagra elsewhere in that state. Two-hundred nine had died at the two orphanages the year before. After the change in eating policies, not a single child died. Not a one had symptoms of pellagra. Similar results in mental institutions and prisons confirmed the theory. By the time physicians were blaming an “outbreak” of pellagra at the Spartan Mill Village on problems with the sanitation system, Goldberger and Wheeler were prepared to test their theory with their lives. Each injected blood from dying pellagra victims into their own blood streams. They took powders ground from skin scales and other parts of pellagra victims’ bodies, in an effort to prove once and for all that pellagra is not contagious. They finally convinced the scientific community. Civilization in general was a little slower in accepting the idea, but pellagra’s days were numbered in the Southern United States. Goldberger was called into the Army, while the Public Health Service instructed Wheeler to carry on with the program. He went throughout several states in the Southeast, proving again and again that fresh milk and fresh meat, eaten regularly, could defeat pellagra. He contributed research data to the fund that produced the science of vitamins and the practice of nutrition. Wheeler retired 42 years ago because of his health. He settled in Spartanburg in 1933. The National Broadcasting System made a dramatic program in 1932 based on the desperate fight Goldberger and Wheeler engaged in to combat pellagra. Books, stories and TV shows have since evolved from that adventure. When television first went into distribution in the Southeast, NBC gave Wheeler a receiver, sending a technician down from Charlotte to set up the instrument, since there were few in Spartanburg experienced in the new art. On the subsequent anniversaries of the cure of the South’s most tenacious killer, various of the region’s newspapers have published special sections devoted to the retelling of the event. Sunday sections appeared in The Atlanta Journal-Constitution and the Columbia State-Record. The New Orleans Times-Picayune published an extra in commemoration of the event. Pellagra still occurs in Italy, Egypt, parts of France and Spain and in the Caribbean countries. The encyclopedia is very descriptive in listing the symptoms of pellagra: “A person who has pellagra is tired and nervous. He does not like to exert himself. The patient’s skin is very pale. After being out in the sun he usually has bright red blotches on his skin. This leaves the skin thick and tough. The patient also suffers from indigestion, diarrhea and constipation. The tongue becomes red and swollen and the throat may burn. Cases of pellagra that are not treated can lead to insanity.” Many old Southern families can remember a member who died of pellagra, or who “was never the same again” after a bout with the disease. While hundreds of thousands of men were overseas fighting “the war to end all wars,” Goldberger and Spartanburg’s George Wheeler were making the world at home safe.

Medical: Atlanta Constitution

July 30, 1914

Headline: Surgeons Recommended

Washington, July 29. -- Secretary McAdoo today recommended to the president the appointment of the following as assistant surgeons in the public health service: Clarence H. Waring, Montrose, Miss.; George A. Wheeler, Higgins, N. C.; Henry C. Yarborough, Montgomery, Ala. and Roland E. Pellagra

Pellagra

Goldberger, Joseph and G.A. Wheeler. The Experimental Production of Pellagra in Human Subjects by Means of Diet. Washington: Government Printing Office, 1920. (Hygienic Laboratory Bulletin)

In 1914, Dr. Joseph Goldberger was sent to the South to find a cure for pellagra. At the time pellagra was thought to be an infectious disease. Goldberger traveled throughout Georgia, South Carolina and other southern states observing employees in hospitals, asylums, and orphanages, yet he never contracted the disease. He believed that diet and pellagra were related and wrote in September 1914, "No pellagra develops in those who consume a mixed, well-balanced diet." Carefully controlled dietary studies in orphanages confirmed this theory and in a classic experiment in a convict camp in Mississippi, Goldberger produced the disease experimentally by diet. Experiments on himself and co-workers showed that it was impossible to transmit the disease from one person to another. Goldberger was convinced that the solution lay with chemists and experimental nutritionists. Foods were analyzed, and Goldberger and his associates began experimental studies with dogs. In 1926, the pellagra-preventive factor was reported to be a member of the B-group of vitamins. In October 1928, Goldberger gave his last public address on pellagra at The American Dietetic Association. He died the following January. Nine years later, a researcher at the University of Wisconsin identified nicotinic acid as the curative factor for pellagra. Wynne, Coffeyville, Miss.

II. HISTORY OF MEDICINE  back to top

Pellagra

In 1914, pellagra was thought to be an infectious disease. In order to find a cure for pellagra, Dr. Joseph Goldberger traveled throughout the South observing employees in hospitals, asylums, and orphanages. Goldberger never "contracted" the disease and concluded that diet and pellagra were related. He wrote in September 1914, "No pellagra develops in those who consume a mixed, well-balanced diet." Carefully controlled dietary studies in orphanages confirmed this theory and in a classic experiment in a convict camp in Mississippi, Goldberger produced the disease experimentally by diet. Additional experiments on himself and co-workers showed that it was impossible to transmit the disease from one person to another. Goldberger was convinced that the solution lay with chemists and experimental nutritionists. Foods were analyzed, and Goldberger and his associates began experimental studies with dogs. In 1926, the pellagra-preventive factor was reported to be a member of the B-group of vitamins. In October 1937, a researcher at the University of Wisconsin identified nicotinic acid (niacin) as the curative factor for pellagra. See: Goldberger, Joseph and G.A. Wheeler. The Experimental Production of Pellagra in Human Subjects by Means of Diet. Washington: Government Printing Office, 1920. (Hygienic Laboratory Bulletin)

Paper 9: Pellagra Is Not Infectious! (Goldberger, 1916)

Presented by Leslie M. Klevay, U.S. Department of Agriculture, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202 and Robert E. Olson, College of Medicine, University of South Florida, Tampa, FL 33606 as part of the mini-symposium "Experiments That Changed Nutritional Thinking" given at Experimental Biology 96, April 16, 1996, in Washington DC.

Microbiology was transforming medicine at the end of the Victorian era. By the time Funk coined the term "vitamine" in 1912, the causative organism for tuberculosis had been known for 30 years. It is not surprising that infection was considered more likely than dietary deficiency to be the cause of pellagra. Both toxicity and heredity, two other causes of disease known at the turn of the century, had also been suggested.

Dementia, dermatitis, diarrhea and finally death associated with a diet of meat, maize and molasses described the pellagra syndrome. Unfortunately, the "meat" consumed by poor people was high in fat and low in protein. The dermatitis is photosensitive and confined to the areas of skin exposed to sunlight; Cásal's (1691-1759) necklace is the eponym attached to "the area of erythema and pigmentation around the neck in pellagra" (Terris 1964). The dementia was usually of the manic-depressive type and severe enough to justify admission to a mental institution.

Joseph Goldberger, who contributed extensively to our understanding of the causes of pellagra, was born in Austria in 1874 and immigrated with his parents to the United States in the 1880s. He grew up in New York City and entered the City College of New York as a high school graduate in 1890 to study engineering but changed his field to medicine two years later by enrolling at the Bellevue Hospital Medical College. He obtained his MD degree in 1895 and after interning for one year and practicing medicine in New York and Pennsylvania for three additional years, he joined the U.S. Public Health Service in 1899. He served as a quarantine officer in various ports including New Orleans, Tampico, Veracruz and Havana and studied yellow fever and typhus transmission by mosquitoes in those areas. In 1909, he solved the cause of Schamberg's disease, a pigmented dermatitis, prevalent in crew members on private yachts and in men living in private dwellings and boarding houses in the Philadelphia area. Goldberger and Schamberg (1909) observed that these men slept on straw mattresses, and they finally identified a mite (Pediculoides ventricosus) as the vector for the disease. Thus, Goldberger had considerable experience in epidemiology and knowledge of infectious diseases when he was assigned by the Surgeon General in 1913 to undertake a study of the causation of pellagra.

Pellagra was not recognized as a problem in the United States until early in the 20th century. In 1912, Lavender of the U.S. Public Health Service estimated that more than 25,000 cases of pellagra had occurred in the United States in the previous five years and that the case fatality rate was 40%. The dominant thinking in the United States at the time Goldberger began his investigations was that pellagra was an infectious disease. As a result of studies in South Carolina, the Thompson-McFadden Pellagra Commission concluded in 1913 that "1) The supposition that the ingestion of good or spoiled maize is the essential cause of pellagra is not supported by our study; and 2) Pellagra is in all probability a specific infectious disease communicable from person to person by means at present unknown." These conclusions were elaborated by Siler et al. (1914).

In less than three months after beginning his investigation, Goldberger (1914) published his first paper on pellagra. In a document of a little over three pages, Goldberger summarized the epidemiology of the disease as follows. Pellagra cannot be communicable. The cause is dietary. Prevention should result from a "reduction in cereals and vegetables and canned foods that enter to a large extent in the dietary of many of the people in the South and an increase in fresh animal food component such as fresh meats, eggs and milk." In support of these views Goldberger pointed out that 1) in institutions where pellagra was prevalent, no case had ever occurred in nurses or attendants; 2) the disease was essentially rural; and 3) it was associated with poverty, which in turn was associated with a diet deficient in animal foods.

These conclusions, however, were reached by epidemiologic methods involving the association of variables and did not constitute proof of the etiology of the disease. Goldberger and his colleagues then proceeded to attempt 1) to cure pellagra by changing the diet of pellagrins to one rich in animal foods and 2) to demonstrate by direct studies the possible infectivity of secretions, scales and excreta from pellagrins. A year after publishing his first paper on pellagra, Goldberger and his coworkers demonstrated in back-to-back papers (Goldberger et al. 1915, Willets 1915) that pellagra could be prevented in institutionalized patients by a diet that included generous amounts of milk, eggs, meat, beans and peas and that pellagra could be successfully treated by the same regimen.

The second part of Goldberger's plan was to demonstrate the nontransmissability of pellagra by contact with nasopharyngeal secretions, blood and excreta from pellagrins (Goldberger 1916). In a heroic study on themselves conducted by Goldberger, Sydenstricker, Tanner, Wheeler, Willets, Goldberger's wife and an additional 10 volunteers, defibrinated blood, nasopharyngeal secretions, feces, urine and dermatitic scales were administered enterally and parenterally in an attempt to cause pellagra. It must be noted that physicians in the public health service at that time had learned to accept such exposures as the risk of dealing with infectious diseases, and in fact Goldberger himself had contracted both yellow fever and typhus from his previous work. Various tissues, nasal secretions and excreta were obtained from 17 cases of pellagra of various grades of severity, including three fatal cases. Goldberger and Wheeler themselves were the first subjects, each receiving 5 mL of the defibrinated blood by intramuscular injection and also secretions. Three days later, Goldberger ate feces from an acutely ill patient together with the urine and dermatitis scales from two other patients. As a result, Goldberger developed diarrhea that lasted for about a week, but despite this both he and Wheeler joined three other volunteers for a similar round of tests with both injections of defibrinated blood from three patients and the oral consumption of scales and excreta. To maximize the chance of catching any infection from stools, they used fresh fecal material from the rectum of pellagrins by using an enema and then blended material from five subjects into pills that were consumed by the volunteers. The volunteers also took sodium bicarbonate before and after consuming these materials to reduce the acidity of the stomach to prevent a possible bacteriocidal action of gastric juice. Mrs. Goldberger received one injection of blood. Both Goldberger and Wheeler felt stiffness after the intramuscular injections, and several volunteers felt nauseous after ingestion of feces. Nonetheless, after five to seven months none showed any sign of pellagra. Because Goldberger's group had failed to demonstrate any transmissibility of an infectious agent to themselves from pellagrins and had demonstrated both the preventative and curative action in pellagrins of diets rich in animal foods, they felt secure in their conclusion that the disease was dietary and not infectious. Nonetheless, they conducted another epidemiologic study of seven cotton mill villages in South Carolina beginning in 1916, which showed that the disease was not high in villages with poor sanitation but was high in villages with poor diets.

In 1920, the question remaining was: What was the agent in animal foods that prevented pellagra? Because the biological value of animal protein was in general better than the values for proteins in cereals and vegetables, Goldberger and Tanner (1922) proposed that an amino acid might be the pellagra preventative factor. Tanner actually conducted a trial of tryptophan in one pellagrous patient, which caused marked improvement of the dermatitis but little change in the diarrhea. He reported the finding in a progress report to Goldberger, but the result was not followed up (Tanner 1921, quoted by Hundley 1954). Goldberger also tested various foods in an attempt to cure black tongue, the pellagrous analogue in dogs.

Goldberger died prematurely at age 55 in 1929. He thus didn't live to see the cure of black tongue with niacin as reported by Elvehjem et al. in 1937, although Goldberger and Sebrell (1930) did induce remission of this canine disease with liver extract. His idea that amino acids were critical in the pathogenesis of pellagra was confirmed by a finding by Krehl et al. (1945), who proved that nicotinic acid could be formed from tryptophan. Subsequently Vilter et al. (1949) showed that tryptophan would cure pellagra in humans.

In summary, Goldberger was a well-trained physician, a brilliant epidemiologist and an imaginative clinical investigator. He studied a variety of infectious diseases and pellagra, which was not infectious, with a multidisciplinary approach that included epidemiology. He is still lauded as a exemplar of clinical epidemiology (Elmore and Feinstein 1994).

Literature Cited

    * Elmore J. G., Feinstein A. R. Joseph Goldberger; an unsung hero of American clinical epidemiology. Ann. Intern. Med. 1994; 121:372-375[Abstract/Free Full Text]

    * Elvehjem C. A., Madden R. J., Strong F. M., Wooley D. W. Relation of nicotinic acid and nicotinic amide to canine black tongue. J. Am. Chem. Soc. 1937; 59:1767-1768

    * Goldberger J. The etiology of pellagra: the significance of certain epidemiological observations with respect thereto. Public Health Rep. 1914; 29:1683-1686

    * Goldberger J. The transmissibility of pellagra: experimental attempts at transmission to the human subject. Public Health Rep. 1916; 31:3159-3173

    * Goldberger J., Schamberg J. F. Epidemic of an urticarioid dermatitis due to a small mite (Pediculoides ventricosus) in the straw of mattresses. Pub. Health Rep. 1909; 24:973-975

    * Goldberger J., Sebrell W. H. The black tongue preventive value of Minot's liver extract. Public Health Rep. 1930; 45:3064-3070

    * Goldberger J., Tanner W. F. Amino acid deficiency probably the etiologic factor in pellagra. Public Health Rep. 1922; 37:462-486

    * Goldberger J., Waring C. H., Willets D. G. A test of diet in the prevention of pellagra. South. Med. J. 1915; 8:1043-1044

    * Goldberger J., Wheeler G. A., Sydenstricker E. A study of the diet on nonpellagrous and of pellagrous households in textile mill communities in South Carolina in 1916. J. Am. Med. Assoc. 1918; 71:944-949

    * Krehl W. A., Tepley L. J., Sarma P. S., Elvehjem C. A. Growth retarding effects of corn in nicotinic acid-low rations and its counteraction by tryptophan. Science 1945; 101:489-491

    * Siler J. F., Garrison P. E., MacNeal W. J. Pellagra, a summary of the first progress report of the Thompson-McFadden Commission. J. Am. Med. Assn. 1914; 62:8-12

    * Tanner, W. F. (1921) Progress report to Goldberger (unpublished and cited by Hundley in Sebrell, W. H. & Harris, R. S. (1954) The Vitamins: Chemistry, Physiology, Pathology, Volume II, page 553. Academic Press, New York, NY.

    * Terris, M. (1964) Goldberger on Pellagra. Louisiana State University Press, Baton Rouge, LA.

    * Vilter R. W., Mueller J. F., Bean W. B. The therapeutic effect of tryptophan in human pellagra. J. Lab. Clin. Med. 1949; 34:409-413

* Willets D. G. The treatment of pellagra by diet. South. Med. J. 1915; 8:1044-1047

Experimental pellagra in the human subject brought about by a restricted diet. With G. A.  Wheeler. Pub. Health Rep. 30:3336-3339, 1915. 

Experimental pellagra in white male convicts. With G. A. Wheeler, Arch. Int. M. 25: 451471, 1920.

The experimental production of pellagra in human subjects by means of diet. With G. A.  Wheeler. Washington, Govt. Print. Off., 1920. (Hygienic Laboratory Bulletin no. 120)

 A further study of butter, fresh beef, and yeast as pellagra preventatives, with  consideration of the relation of factor P-P of pellagra (and black tongue of dogs) to  vitamin B. With G. A.Wheeler, R. D. Lillie, and L. M. Rogers. Pub. Health Rep.41: 297318, 1926. “Anti-pellagra vitamin.” Garrison nos. 1057 and 3758.

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Blair Wheeler