He found that muscle seizure (tetany) was due to abrogation of parathyroid glands, and that injection of calcium salt could restore the condition.

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.

(His brother John Bruce MacCallum would also become a physician but died at the age of thirty due to tuberculosis).

At 15 years of age he entered the University of Toronto, where his main interest was in Greeks, among his subjects such as zoology, chemistry, physics and geology.

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.

[10] 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."

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.

He went back to procure the bird itself and later found that the blood sample contained highly active malarial parasites.

[14] He diagnosed in the next summer research that protozoan infections such as Halteridium and Proteosoma were symptomatically similar, and produced pathogenic lesions as in human malaria.

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...

[16][17] This was almost a Nobel Prize-winning work because the next year Ronald Ross of the Indian Medical Service demonstrated the transmission of bird malarial parasite (then Proteosoma but now Plasmodium relictum) by a mosquito (then Culex fatigans, but now Culex quinquefasciatus),[18][19][20] for which Ross won the Nobel Prize for Physiology or Medicine in 1902.

[23][24] 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.

MacCallum showed that most of the prevailing hypotheses were wrong (such as connection through stomata, pores or canaliculi) and that the tissues had no special interconnecting link.

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 in contrast to popular belief; and that injection of calcium salt could completely restore all the symptoms of tetany.

[30][31][32] From 1909 MacCallum investigated a unique tetanic condition called gastric tetany, in which parathyroid glands are normal.

[33][34][35] During medical course at the Johns Hopkins MacCallum and classmate Joseph L. Nichols had rented a house at 1200 Guilford Avenue and as a housewarming celebration invited their teachers William H. Welch and William Osler, other faculty members, and friends to the house and entertained them with a keg of beer.

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."