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William George MacCallum (18 April 1874 – 3 February 1944) was a Canadian-American physician and pathologist. He was of Scottish descent and was born in
Dunnville Dunnville is an unincorporated community located near the mouth of the Grand River in Haldimand County, Ontario, Canada near the historic Talbot Trail. It was formerly an incorporated town encompassing the surrounding area with a total populat ...
village in Canada, where his father was a physician. He was educated at the
University of Toronto The University of Toronto (UToronto or U of T) is a public research university in Toronto, Ontario, Canada, located on the grounds that surround Queen's Park. It was founded by royal charter in 1827 as King's College, the first institution ...
. He graduated with BA in 1894. Initially inclined towards Greeks as academic career, his father influenced him to enter medicine. He joined the second year of the first batch of medicine course in the
Johns Hopkins Medical School The Johns Hopkins University School of Medicine (JHUSOM) is the medical school of Johns Hopkins University, a private research university in Baltimore, Maryland. Founded in 1893, the School of Medicine shares a campus with the Johns Hopkins Hospi ...
, and became one of the first graduates of the institute in 1897. He was appointed assistant resident of pathology of the medical school in 1897, resident pathologist in 1901, soon after Associate Professor, and full Professor in 1908. Between 1909 and 1917 he held a twin position of Professor of Pathology at
Columbia University Columbia University (also known as Columbia, and officially as Columbia University in the City of New York) is a private research university in New York City. Established in 1754 as King's College on the grounds of Trinity Church in Manhatt ...
and the
NewYork–Presbyterian Hospital The NewYork-Presbyterian Hospital is a nonprofit academic medical center in New York City affiliated with two Ivy League medical schools, Cornell University and Columbia University. The hospital comprises seven distinct campuses located in the New Y ...
. From 1917 to 1943 he held the Chair of Pathogy at
Johns Hopkins University Johns Hopkins University (Johns Hopkins, Hopkins, or JHU) is a private university, private research university in Baltimore, Maryland. Founded in 1876, Johns Hopkins is the oldest research university in the United States and in the western hem ...
. MacCallum discovered the existence of two forms (now known to be male gamete or microgametocyte and female gamete or macrogametocyte) of
malarial parasite ''Plasmodium'' is a genus of unicellular eukaryotes that are obligate parasites of vertebrates and insects. The life cycles of ''Plasmodium'' species involve development in a blood-feeding insect host which then injects parasites into a verteb ...
in birds in 1897. In 1899 he and T.W. Hastings discovered a new species of pathogenic
Gram-positive bacteria In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bact ...
called ''Micrococcus zymogenes''. He was the first to describe the structural and functional relationship between
lymphatic system The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphatic or lymphoid o ...
and
connective tissue Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...
. In 1905 he discovered that
thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thy ...
and
parathyroid Parathyroid glands are small endocrine glands in the neck of humans and other tetrapods. Humans usually have four parathyroid glands, located on the back of the thyroid gland in variable locations. The parathyroid gland produces and secretes par ...
glands had completely different functions. He found that muscle seizure (
tetany Tetany or tetanic seizure is a medical sign consisting of the involuntary contraction of muscles, which may be caused by disorders that increase the action potential frequency of muscle cells or the nerves that innervate them. Muscle cramps cause ...
) was due to abrogation of parathyroid glands, and that injection of
calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...
salt could restore the condition. This directly laid the understanding of the role of calcium in
muscle contraction Muscle contraction is the activation of tension-generating sites within muscle cells. In physiology, muscle contraction does not necessarily mean muscle shortening because muscle tension can be produced without changes in muscle length, such as ...
. In 1909 he discovered that a disease gastric tetany was not due to parathyroid functions, but because of blockage of the stomach-intestine connection called
pylorus The pylorus ( or ), or pyloric part, connects the stomach to the duodenum. The pylorus is considered as having two parts, the ''pyloric antrum'' (opening to the body of the stomach) and the ''pyloric canal'' (opening to the duodenum). The ''pylori ...
. He wrote a definitive textbook ''A Textbook of Pathology'' which ran several editions and is still in print. A histochemical staining technique for
Gram-negative bacteria Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...
called MacCallum-Goodpasture stain is jointly named after him and the co-discoverer
Ernest William Goodpasture Ernest William Goodpasture (October 17, 1886 – September 20, 1960) was an American pathologist and physician. Goodpasture advanced the scientific understanding of the pathogenesis of infectious diseases, parasitism, and a variety of ricketts ...
. A condition in rheumatic heart disease MacCallum plaque is named after him.


Early life and education

William MacCallum was born in Dunnville village to a physician father George A. MacCallum and mother Florence Eakins. His grandfather George MacCallum had emigrated from Scotland to Canada in his youth. He was the second of four children, with an elder sister, and a younger brother and a sister. (His brother John Bruce MacCallum would also become a physician but died at the age of thirty due to
tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...
). He entered Dunnville public school and high school for his early education. He spent much of his free time accompanying his father, who was a general practitioner, in visiting resident patients. At 15 years of age he entered the
University of Toronto The University of Toronto (UToronto or U of T) is a public research university in Toronto, Ontario, Canada, located on the grounds that surround Queen's Park. It was founded by royal charter in 1827 as King's College, the first institution ...
, where his main interest was in Greeks, among his subjects such as zoology, chemistry, physics and geology. He graduated in 1894. His father's persuasion that he should take up medicine was his career-making event as he wanted to continue with Greeks for himself. By then he learned that the
Johns Hopkins University Johns Hopkins University (Johns Hopkins, Hopkins, or JHU) is a private university, private research university in Baltimore, Maryland. Founded in 1876, Johns Hopkins is the oldest research university in the United States and in the western hem ...
had started Medical School in 1893 at
Baltimore Baltimore ( , locally: or ) is the List of municipalities in Maryland, most populous city in the U.S. state of Maryland, fourth most populous city in the Mid-Atlantic (United States), Mid-Atlantic, and List of United States cities by popula ...
with its first batch of medical students. He applied for the medical course and was allowed to join the first batch, who were already in their second year, as it was decided that his education at Toronto was considered equivalent to the first year medical course. He was therefore member of the first class at Johns Hopkins who earned MD degree in 1897.


Career

MacCallum served a one-year internship at
Johns Hopkins Hospital The Johns Hopkins Hospital (JHH) is the teaching hospital and biomedical research facility of the Johns Hopkins School of Medicine, located in Baltimore, Maryland, U.S. It was founded in 1889 using money from a bequest of over $7 million (1873 mo ...
during 1897-1898, and was appointed assistant resident pathologist under
William Henry Welch William is a male given name of Germanic origin.Hanks, Hardcastle and Hodges, ''Oxford Dictionary of First Names'', Oxford University Press, 2nd edition, , p. 276. It became very popular in the English language after the Norman conquest of Eng ...
at the Johns Hopkins University. In 1900 he worked with
Felix Jacob Marchand Felix Jacob Marchand (22 October 1846 – 4 February 1928) was a German pathologist born in Halle an der Saale. He studied medicine in University of Berlin, Berlin, and later became an assistant at the pathological institute in University of Hal ...
at the
University of Leipzig Leipzig University (german: Universität Leipzig), in Leipzig in Saxony, Germany, is one of the world's oldest universities and the second-oldest university (by consecutive years of existence) in Germany. The university was founded on 2 Decemb ...
in Germany. He returned to Baltimore in 1901 to become resident patholosgist and Associate Professor of Pathology. He was promoted to full Professor in 1908. Between 1909 and 1917 he was invited to Columbia University and NewYork–Presbyterian Hospital, where he simultaneously worked as Professor and pathologist respectively. In 1917 Welch resigned from the Chair of Pathology at Johns Hopkins University to assume the new post of Director at the School of Hygiene and Public Health. MacCallum was selected to take the vacant Chair, which he occupied until his retirement in 1943. He was designated Baxler Professor of Pathology in the university and pathologist to the Johns Hopkins Hospital.


Achievements


Malariology

While he was studying in Baltimore, MacCallum used to spend his summer vacation at home in Dunville, where he and his father had, what he referred to as "a makeshift laboratory in the woodshed." They would study specimens of all sorts collected from the country side. It was during his last year at Johns Hopkins Medical School, in the summer of 1896 that he made a pivotal discovery in
malariology Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects humans and other animals. Malaria causes Signs and symptoms, symptoms that typically include fever, fatigue (medical), tiredness, vomiting, and headaches. In se ...
. It was the period of intense research to unravel the mode of transmission of malarial parasite, for which the leading contenders were British and Italian physicians. One day MacCallum collected blood sample far from his home, and in his home laboratory he observed active parasites called ''Halteridium columbae'' (but now considered as ''
Haemoproteus columbae ''Haemoproteus columbae'' is a species of blood parasite related to ''Plasmodium'' and other malaria parasites. Phylogenetic relationships among the Haemosporidia ''Haemoproteus columbae'' is a true member of the genus ''Haemoproteus'', basal t ...
'') among the
blood cells A blood cell, also called a hematopoietic cell, hemocyte, or hematocyte, is a cell produced through hematopoiesis and found mainly in the blood. Major types of blood cells include red blood cells (erythrocytes), white blood cells (leukocytes), a ...
. He went back to procure the bird itself and later found that the blood sample contained highly active malarial parasites. His reported his findings before the Medical Society of Johns Hopkins Hospital in November 1896, was published in 1897 in the ''Bulletin of the Johns Hopkins Hospital'' and more complete form in ''
The Lancet ''The Lancet'' is a weekly peer-reviewed general medical journal and one of the oldest of its kind. It is also the world's highest-impact academic journal. It was founded in England in 1823. The journal publishes original research articles, ...
''. He diagnosed in the next summer research that
protozoan infections Protozoan infections are parasitic diseases caused by organisms formerly classified in the kingdom Protozoa. They are usually contracted by either an insect vector or by contact with an infected substance or surface and include organisms that are ...
such as ''Halteridium'' and ''Proteosoma'' were symptomatically similar, and produced pathogenic lesions as in human malaria. He further discovered that there were two groups of the parasite, one which are non-motile "granular" (now called microgametocytes) and one motile "hyaline" (macrogametocytes); and that the motile groups were flagellated cells having four or more arms that could fuse with the non-motile forms (the process of
fertilisation Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...
) to form non-motile bodies called vermicule (but now called
ookinete Apicomplexans, a group of intracellular parasites, have Biological life cycle, life cycle stages that allow them to survive the wide variety of environments they are exposed to during their complex life cycle. Each stage in the life cycle of an a ...
). This was the first description of sexual dimorphism and reproduction in the life cycle of prorotozoans. In his 1898 paper he gave a critical deduction that the motile forms were male gametes, the non-motile female gametes, and the vermicule the
zygote A zygote (, ) is a eukaryotic cell formed by a fertilization event between two gametes. The zygote's genome is a combination of the DNA in each gamete, and contains all of the genetic information of a new individual organism. In multicellula ...
(which were later proven to be true). He concluded with foresight that "This is a process which we might have expected and which I am confident will be found to occur in the case of the human malaria parasites... It is evidently for the human being what is foreshadowed by the organism of the bird. This was almost a Nobel Prize-winning work because the next year
Ronald Ross Sir Ronald Ross (13 May 1857 – 16 September 1932) was a British medical doctor who received the Nobel Prize for Physiology or Medicine in 1902 for his work on the transmission of malaria, becoming the first British Nobel laureate, and the f ...
of the
Indian Medical Service The Indian Medical Service (IMS) was a military medical service in British India, which also had some civilian functions. It served during the two World Wars, and remained in existence until the independence of India in 1947. Many of its officer ...
demonstrated the transmission of bird malarial parasite (then ''Proteosoma'' but now ''
Plasmodium relictum ''Plasmodium relictum'' is a species in the genus ''Plasmodium,'' subgenus '' Haemamoeba''. It is a parasite, and the most common cause of malaria in birds. Like all ''Plasmodium'' species, ''P. relictum'' has both vertebrate and insect host ...
'') by a mosquito (then ''Culex fatigans'', but now ''
Culex quinquefasciatus ''Culex'' is a genus of mosquitoes, several species of which serve as vectors of one or more important diseases of birds, humans, and other animals. The diseases they vector include arbovirus infections such as West Nile virus, Japanese encep ...
''), for which Ross won the
Nobel Prize for Physiology or Medicine The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, according ...
in 1902.


Bacteriology

In 1899 MacCallum and T.W. Hastings described a new species of pathogenic Gram-positive bacterium which they named ''Micrococcus zymogenes''. The bacterium was discovered to be the causative agent of heart infection (acute
endocarditis Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves. Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, or the ...
). The bacterium was a very small, occurred mainly in pairs, sometimes in short chains, and developed in small, pale, grayish-white colonies. It was uniquely capable of
fermenting Fermentation is a metabolic process that produces chemical changes in organic substrates through the action of enzymes. In biochemistry, it is narrowly defined as the extraction of energy from carbohydrates in the absence of oxygen. In food ...
milk, hence, the name ''zymogenes''.


Physiology

At the University of Leipzig in 1900 MacCallum studied the lymphatic system from the skin of pig embryo, and completed the work in Baltimore after two years. At the time the connection between lymphatic system and connective tissues was not known, and there were many speculations, of which the dominant idea was that they were directly linked. MacCallum showed that most of the prevailing hypotheses were wrong (such as connection through
stomata In botany, a stoma (from Greek ''στόμα'', "mouth", plural "stomata"), also called a stomate (plural "stomates"), is a pore found in the epidermis of leaves, stems, and other organs, that controls the rate of gas exchange. The pore is bor ...
, pores or canaliculi) and that the tissues had no special interconnecting link. Instead, solid particles are transported between them through cell transfer (
phagocytosis Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is ...
). The lymphatic vessels were made up of endothelial lining structurally similar to normal blood vessels. In 1903 MacCallum started investigating thyroid and parathyroid secretions, for which there were confusion and uncertainty at the time. He discovered that the
endocrine glands Endocrine glands are ductless glands of the endocrine system that secrete their products, hormones, directly into the blood. The major glands of the endocrine system include the pineal gland, pituitary gland, pancreas, ovaries, testes, thyroid g ...
were of completely independent functions. He found that muscle seizure (tetany) thought to be due to surgery on thyroid was actually due to injury or removal of parathyroid glands; parathyroid contained no
iodine Iodine is a chemical element with the symbol I and atomic number 53. The heaviest of the stable halogens, it exists as a semi-lustrous, non-metallic solid at standard conditions that melts to form a deep violet liquid at , and boils to a vi ...
in contrast to popular belief; and that injection of calcium salt could completely restore all the symptoms of tetany. His findings were published in 1905. In 1909, with Carl Voegtlin he finally established the direct importance of calcium in tetany, and thereby muscle contraction. From 1909 MacCallum investigated a unique tetanic condition called gastric tetany, in which parathyroid glands are normal. The disease was due to obstruction at the pylorus region (near the intestine) of the stomach. He found in dogs that under gastric tetany, gastric
hydrochloric acid Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution with a distinctive pungent smell. It is classified as a strong acid Acid strength is the tendency of an acid, symbol ...
was lost, and the chlorine in the blood plasma was reduced causing severe
electrolyte imbalance Electrolyte imbalance, or water-electrolyte imbalance, is an abnormality in the concentration of electrolytes in the body. Electrolytes play a vital role in maintaining homeostasis in the body. They help to regulate heart and neurological function, ...
. This further caused increased
electrical excitability Electricity is the set of physical phenomena associated with the presence and motion of matter that has a property of electric charge. Electricity is related to magnetism, both being part of the phenomenon of electromagnetism, as described ...
of
neurons A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
leading to increased muscle twitching. In most severe cases violent convulsion occurred and the dogs die. These effects could be easily reversed by injecting chloride salts. His findings were reported before the American Society for Pathology in 1917, and published in full form in 1920.


Pithotomy Club

During medical course at the Johns Hopkins MacCallum and classmate Joseph L. Nichols had rented a house at 1200
Guilford Avenue This is a list of notable streets in the city of Baltimore, Maryland, United States. A B C D E F G H Heath St. Route 64. (MTA Maryland) K L M N O P R Ramsay st S U W Y Numbered streets In Balt ...
and as a housewarming celebration invited their teachers
William H. Welch William Henry Welch (April 8, 1850 – April 30, 1934) was an American physician, pathologist, bacteriologist, and medical-school administrator. He was one of the "Big Four" founding professors at the Johns Hopkins Hospital.William Osler Sir William Osler, 1st Baronet, (; July 12, 1849 – December 29, 1919) was a Canadian physician and one of the "Big Four" founding professors of Johns Hopkins Hospital. Osler created the first Residency (medicine), residency program for spec ...
, other faculty members, and friends to the house and entertained them with a keg of beer. These frequent gatherings evolved into a sort of club, for which MacCallum coined the name Pithotomy Club (from a combination of two Greek words ''
pithos Pithos (, grc-gre, πίθος, plural: ' ) is the Greek name of a large storage container. The term in English is applied to such containers used among the civilizations that bordered the Mediterranean Sea in the Neolithic, the Bronze Age and ...
'', meaning vessel, and ''otomos'', meaning to open, which was taken to mean "to tap a keg"). The club's constitution, written in 1897, states its mission as to "facilitate the advancement of its members in the art and science of medicine by the promotion of social intercourse between the faculty and students of the Society," in addition to a more humorous objective of "the promotion of vice among the virtuous, virtue among the vicious, and good fellowship among all." It became one of the longest surviving academic clubs, and longest running medical club in history, and most of its members became successful doctors, including
George Hoyt Whipple George Hoyt Whipple (August 28, 1878 – February 1, 1976) was an American physician, pathologist, biomedical researcher, and medical school educator and administrator. Whipple shared the Nobel Prize in Physiology or Medicine in 1934 with George ...
who received the 1943
Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...
. After 95 years in 1992 it became
defunct Defunct (no longer in use or active) may refer to: * ''Defunct'' (video game), 2014 * Zombie process or defunct process, in Unix-like operating systems See also * * :Former entities * End-of-life product * Obsolescence Obsolescence is t ...
and the club building was donated to and absorbed by Johns Hopkins Medical School.


Honours and recognition

*Honorary Fellow of the
Royal Society of Medicine The Royal Society of Medicine (RSM) is a medical society in the United Kingdom, headquartered in London. History The Society was established in 1805 as Medical and Chirurgical Society of London, meeting in two rooms in barristers’ chambers ...
*Corresponding member of Societas Regia Medicorum Budapestinesis *Honorary Member of the Societe d' Endocrinologie of Paris *Honorary Member of the Pathological Society of Great Britain and Ireland *Elected President of the
International Academy of Pathology The International Academy of Pathology, originally called the International Association of Medical Museums (IAMM), is an institution dedicated "to the advancement of Pathology". In 1906, it was established by Dr. William Osler and Maude Abbott Mau ...
during 1908-1909 *Elected President of the International Association of Medical Museums during 1908-1909 *Elected member of the US National Academy of Sciences in 1921 *Kober Lecturer by the Association of American Physicians in 1940 *McCullum-Goodpasture stain is jointly named after him and Ernest William Goodpasture. *An eponymous MacCallum plaque is for a rheumatic heart condition.


Personal life and death

MacCallum never married. He loved to travel and visited France, Germany, Italy, West Indies, South America, South Africa, Australia, India, Siam, Burma, Singapore, Japan, and the South Sea Islands. Towards the end of 1943 he had serious illness for which he went to Florida. He was soon inflicted with
hemiplegic Hemiparesis, or unilateral paresis, is weakness of one entire side of the body ('' hemi-'' means "half"). Hemiplegia is, in its most severe form, complete paralysis of half of the body. Hemiparesis and hemiplegia can be caused by different medic ...
paralysis and his condition deteriorated, and died on 3 February 1944.


References


External links

*
Biography at Canadian EncyclopediaBrief biography at United States & Canadian Academy of PathologyBrief biography at Pathology of Johns Hopkins
{{DEFAULTSORT:MacCallum, William George Canadian people of Scottish descent University of Toronto alumni Columbia University faculty Members of the United States National Academy of Sciences 1874 births 1944 deaths Johns Hopkins University faculty Johns Hopkins University alumni Canadian pathologists Malariologists