Michael Heidelberger and the Beginning of Immunochemistry
Year: 2002
Type: article
Abstract: The Soluble Specific Substance of Pneumococcus. IV. On the Nature of the Specific Polysaccharide of Type III Pneumococcus (Heidelberger, M., and Goebel, W. F. (1926)J. Biol. Chem.70, 613–624) Michael Heidelberger (1888–1991) was a founder of immunochemistry. He was born in New York City and was educated in his early years by his mother. She was able to cover the basic subjects in an hour or two each day leaving time for the classics and music and to wander the city visiting museums and going to the opera (1Heidelberger M. Annu. Rev. Microbiol. 1977; 31 (A “pure” organic chemist’s downward path.): 1-12Crossref PubMed Scopus (11) Google Scholar). He decided to become a chemist at the age of 8. He attended Columbia University receiving his B.S. (1908), A.M. (1909), and Ph.D. (1911) degrees, all in organic chemistry. After a postdoctoral year in Zurich working with Richard Willstater, he returned to New York and was appointed a Fellow of the Rockefeller Institute by Simon Flexner where he would stay until 1927 rising to Associate Member. For the first nine years at Rockefeller, Heidelberger worked with Walter A. Jacobs in a close and productive collaboration synthesizing potential chemotherapeutic drugs. (Walter A. Jacobs was an outstanding natural products alkaloid chemist and the author of a future Journal of Biological Chemistry (JBC) Classic). One great success of the Jacobs-Heidelberger collaboration was the synthesis of tryparsamide, sodium para-phenylglycinamide arsonate, which was effective against African sleeping sickness, i.e. trypanosomiasis. The Belgian government awarded Heidelberger, Jacobs, and their collaborators the Order of Leopold II for this accomplishment (3Cruse J. J. Immunol. 1988; 140 (A centenary tribute. Michael Heidelberger and the metamorphosis of immunologic science.): 2861-2863PubMed Google Scholar). The work featured in this JBC Classic was done in Heidelberger’s last few years at the Rockefeller. He was enlisted by Oswald T. Avery to help identify the “specific soluble substance” of pneumococci. It had been shown by Dochez and Avery (4Dochez A.R. Avery O.T. J. Exp. Med. 1917; 26: 447Crossref Scopus (97) Google Scholar) that the culture fluids of pneumococci contained a substance that precipitates specifically with anti-pneumococci serum. The “soluble specific substance” was also found in the body fluids of infected organisms including humans. Using the laborious purification techniques required before the advent of chromatography, Heidelberger eventually purified the material from Types I, II, and III pneumococci. It was surprising that the material was not protein and contained no nitrogen and was shown to be a polysaccharide. The lack of nitrogen in the antigen made it possible in later work to use the polysaccharide antigen to quantitate the amount of protein, antibody, present in an immunoprecipitate. This work launched Heidelberger’s scientific career in immunology, and he, along with Forrest E. Kendall, worked for many years to quantitatively define the precipitin reaction of polysaccharides and eventually the much more difficult problem of defining the antibody reaction with protein antigens. On advice of colleagues at the Rockefeller, Heidelberger sought an independent position. After a year of reorganizing the chemistry laboratories at Mt. Sinai Hospital, which allowed little time for research, he took a position as Associate Professor in the Department of Medicine at Columbia University College of Physicians and Surgeons where he would serve until the age of 67 and mandatory retirement. During the period at Physicians and Surgeons, Heidelberger and colleagues, including Elvin Kabat, a gifted graduate student and later distinguished immunologist, proved that antibodies were globulins and that specific precipitation, agglutination, and complement fixation were different manifestations of a single antibody. Heidelberger's quantitative work resulted in the preparation of more effective anti-influenza sera that saved the lives of many infants with influenzal meningitis (2Heidelberger M. Annu. Rev. Biochem. 1979; 48 (A pure organic chemist’s downward path: chapter 2—The Years at P. and S.): 1-21Crossref PubMed Scopus (9) Google Scholar, 3Cruse J. J. Immunol. 1988; 140 (A centenary tribute. Michael Heidelberger and the metamorphosis of immunologic science.): 2861-2863PubMed Google Scholar). After leaving Physicians and Surgeons, Heidelberger accepted Selman Wazman's offer of a position at the Institute of Microbiology at Rutgers University and continued his research for another 10 years after which he moved to the Department of Pathology at New York University and continued his research until his death in 1991. His career was devoted to the development of rigorous quantitative methods for the measurement of antibodies and the purification of antibody molecules. It was a career of nearly 80 years! Heidelberger received many awards during his career, including the National Medal of Science and two Lasker Awards (1953 and 1978). In addition to science, Heidelberger was a talented musician and composer. He was also a citizen of the world, a strong spokesman for world peace, supporter of the mission of the United Nations, and a participant in the World Health Organization. He had a particular concern about nuclear proliferation and had a lecture entitled “The Scientist and Survival in an Atomic Era.”
Source: Journal of Biological Chemistry
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1563228551