First
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Dr. George Alexander Wheeler |
Agnes
Elizabeth Kullgran
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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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