He experimented at home by mixing medicines and the very basic ingredients included in children's chemistry sets of the time, until he began his formal training in botany, zoology, physics, and chemistry at the Ethical Culture School, a private high school on New York's Upper West Side founded by the Ethical Culture Society, a Humanist religious movement of which his parents were members.
He played the same two handmade wood instruments, a B flat and an A clarinet, all of his life, taking them with him wherever he went to join in chamber music performances at conferences or at the homes of friends.
His dissertation dealt with quinazoline analogs, alkaloids that his adviser, Marston Taylor Bogert, hoped—wrongly, as Heidelberger proved—would produce useful dyes when combined with phthalic acid.
As a student he supported himself by selling Virginia hams to hotels and wholesale grocers around the city on Friday afternoons, earning up to $50 per week, and by teaching analytical chemistry under Irving Langmuir at Stevens Institute in Hoboken, New Jersey.
Urged on by his parents, Heidelberger after graduation with his Ph.D. arranged for a visit with his former family physician, Samuel J. Meltzer, who had seen him through typhoid fever as a young child and who had since become the first chair of the Department of Physiology at the newly founded Rockefeller Institute of Medical Research.
Meltzer relented, and sent him on to meet with the institute's chemists, Phoebus A. T. Levene, Donald D. Van Slyke, and Walter A. Jacobs, whom Heidelberger found assembled over tea.
Heidelberger took their advice and in 1911 went to Zürich to work for a year in the laboratory of the organic chemist and future Nobel Laureate Richard Willstätter at the Eidgenössische Technische Hochschule.
Heidelberger passed muster, and in September 1912 began working in Walter Abraham Jacobs' laboratory on a derivative of hexamethylene tetramine, a complex that seemed to prolong the life of monkeys suffering from polio, and that Flexner hoped could be adapted for use in humans.
In the summer of 1915, after attending officer training camp in Plattsburgh, New York, for a proposed volunteer army (an outgrowth of the movement to prepare the United States for entry into World War I) and earning a commendation as a marksman, Heidelberger traveled to Lake Kezar in Maine for a vacation.
In 1919 they developed a variant of Paul Ehrlich's "magic bullet" for syphilis, Salvarsan, which proved effective against trypanosomes, the parasites that cause African sleeping sickness.
In 1953 the king of Belgium, colonial ruler of parts of Africa in which African sleeping sickness had been endemic, honored Heidelberger and Jacobs for their discovery.
When Karl Landsteiner, the famous Austrian immunologist and discoverer of human blood groups, arrived at the institute in 1922, Heidelberger embarked with him on studies of the antigenic properties of different types of hemoglobin.
In 1923, Heidelberger and Avery reported that this capsular substance, which determined the specific type of pneumococcus and, with it, its virulence, consisted of polysaccharides, carbohydrate molecules made up of more than three monosaccharide units.
The door to his office, which he likened to "42nd Street and Broadway" because of its traffic, was open for anyone, especially junior researchers, to stop by, discuss matters of science or politics, and seek his advice.
During his 27 years there he used his unique knowledge of polysaccharide antigen chemistry to develop methods, in particular the precipitin reaction, for isolating pure antibodies, which he proved were protein and which he measured in absolute units of weight for the first time.
These findings enabled Heidelberger to develop a much more potent antiserum to meningitis in infants, as well as a simple but effective vaccine against several forms of pneumonia, which was successfully tested among Army Air Force recruits in 1944.