Michael Heidelberger (immunologist)

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Picture by Michael Heidelberger from 1954
Michael Heidelberger, 1954

Michael J. Heidelberger (born  April 29, 1888 in New York City , †  June 25, 1991 ibid) was an American chemist and immunologist . He worked from 1912 to 1927 at the Rockefeller Institute for Medical Research , from 1928 to 1956 as a professor at Columbia University and as a chemist at New York's Presbyterian Hospital , from 1955 to 1964 as a visiting professor at Rutgers University and then until his death as an adjunct professor Professor at New York University .

After Michael Heidelberger had primarily dealt with topics of drug chemistry and chemical analysis at the beginning of his career , he later turned to immunological research. In this area, he primarily investigated the chemical nature of antibodies and antigens as well as the reaction between bacterial polysaccharides and antibodies known as precipitation . In particular, he was able to prove that antibodies are proteins and also laid the foundations for immunochemical analysis methods such as ELISA and RIA .

Based on his research results, Michael Heidelberger is considered to be a co-founder of modern immunobiology and, in particular, quantitative immunochemistry. For his fundamental contributions to immunology, he received the Albert Lasker Award for Basic Medical Research in 1953 , the National Medal of Science in 1967 , the Louisa Gross Horwitz Prize in 1977 and the Albert Lasker Award for Clinical Medical Research in 1978 . He was also a member of the National Academy of Sciences from 1942 and of the Royal Society from 1975 . He was scientifically active until shortly before his death and published a total of 365 scientific papers in over seven decades  .

Life

Education and work at the Rockefeller Institute

Image by Richard Willstätter
Michael Heidelberger spent a year as a post-doctoral student with Richard Willstätter, who later won the Nobel Prize at the ETH in Zurich

Michael Heidelberger was born in the Manhattan borough of New York in 1888 . His father, who was a traveling salesman, and his mother belonged to the middle class . The Jewish-born grandparents were about four decades before his birth in Germany emigrated and had in Idaho settled. His mother insisted that he and his younger brother learn German and French . After taking an early interest in chemistry at school, he began studying chemistry at Columbia University in his hometown in 1905 , where he obtained a BS degree in 1908 and an AM degree a year later . In 1911 he finished his studies at Columbia University with a doctorate in organic chemistry for quinazoline derivatives . He then decided, on the advice of the family doctor, who worked as a physiologist at the Rockefeller Institute for Medical Research , to do research abroad. He went to the Swiss Federal Institute of Technology in Zurich for a year , where he deepened his focus on organic chemistry with work on cyclooctatetraene in the laboratory of the later Nobel Prize winner Richard Willstätter . The time in Zurich remained the longest part of his life that he spent outside of Manhattan until his death.

On his return to the United States, he got a job at the Rockefeller Institute for Medical Research in September 1912. Together with Walter Abraham Jacobs and Simon Flexner , he worked here on the synthesis of therapeutically useful arsenic compounds . During the First World War , Michael Heidelberger trained doctors and technical assistants in laboratory work from 1915 as an officer in the Medical Corps of the United States Army at the Rockefeller Institute. In addition, he continued his research on drug synthesis. After the end of the war, Michael Heidelberger and Walter Jacobs turned to new research topics. During this time, as part of studies on blood pigments with the refrigerated centrifuge, he developed a laboratory device that is still produced by various manufacturers and is in use in laboratories around the world. He received $ 50 from the company that marketed the device for writing the instruction manual. A short time later he began with Karl Landsteiner , who was replaced at the Rockefeller Institute in 1922, and with Oswald Avery and Walther F. Goebel , the Institute pneumococcal explored in the study of the chemical properties of polysaccharides from capsule of bacteria work together .

Research at Columbia University

Image by Elvin Kabat
Elvin A. Kabat (center), first doctoral student and long-time employee of Michael Heidelberger

After his investigations into blood pigments such as hemoglobin brought him into contact with biochemical issues for the first time, Michael Heidelberger dealt with immunological working techniques at the suggestion of Karl Landsteiner. In 1927 he moved to New York's Mount Sinai Hospital , as Simon Flexner was of the opinion that Michael Heidelberger would be in the shadow of outstanding scientists such as Karl Landsteiner, Oswald Avery and Walter Jacobs if he stayed at the Rockefeller Institute. In the following year he became an associate professor of medicine at Columbia University; from 1929 to 1945 he worked there as Associate Professor of Biological Chemistry, from 1945 to 1948 as Professor of Biochemistry and from 1948 to 1956 as Professor of Immunochemistry. At the same time, he also worked as a chemist from 1928 to 1956 at New York's Presbyterian Hospital , a teaching hospital at Columbia University, where he established his own laboratory and, among other things, devoted himself to investigations into thyroglobulin and the purification of antigens from hemolytic streptococci .

The focus of his research, however, was to clarify the nature of the serum components that lead to precipitation with the bacterial capsular polysaccharides, and thus the clarification of the question of whether antibodies are proteins from the class of globulins . As part of these investigations, he and his colleagues developed a quantitative method known as the precipitin reaction for investigating the antigen-antibody reaction . Through these studies, the British immunologist John Marrack , who in 1934 had published an influential work on the chemical nature of antigens and antibodies under the title "The Chemistry of Antigens and Antibodies", became aware of the work of Michael Heidelberger, which resulted in a temporary collaboration and resulted in a lifelong friendship between the two. Together with Elvin A. Kabat , who initially worked as a student in Heidelberg's laboratory and later became his first doctoral student , Michael Heidelberger also worked on improving the precipitin reaction and on investigating the agglutination of bacteria after the addition of antiserum.

The collaboration with microbiologists at the hospital also made important contributions to the clinical application of immunology. Michael Heidelberger succeeded in developing an effective antiserum for the treatment of meningitis in young children. In addition, he was finally able to purify antibodies and prove that they were actually globulins. In 1934 and 1936, with a Guggenheim grant , he spent around six weeks in the laboratory of the later Nobel Prize winner The Svedberg at Uppsala University , where he used the ultracentrifuges constructed by Svedberg to estimate the molecular mass of antibodies and conduct further studies whose protein character was finally able to prove. He then turned to the investigation of the complement , for which it was not known until then whether it was a defined substance or a property of fresh blood.

Active retirement

Image by Selman Waksman
The microbiologist and Nobel Prize winner Selman A. Waksman, who brought Michael Heidelberger to Rutgers University

During the Second World War , Michael Heidelberger was commissioned to deal with the prevention and treatment of anthrax in animals and with the elucidation of the mechanism of action of ricin . In addition, he studied for the prevention of pneumonia that vaccination with bacterial polysaccharides for this purpose industrially by the company ER Squibb & Sons had been made, and the treatment of malaria with antisera that were obtained with the parasites of the respective patient. While the studies on vaccination against pneumococci were positive, the work on malaria therapy did not show any notable success. In 1947 and 1949 he was elected President of the American Association of Immunologists .

Just before he in 1956 at Columbia University at the age of 68 years emeritus was, he went at the invitation of Selman Waksman , the discoverer of the antibiotic streptomycin , as Visiting Professor of Immunochemistry at the Institute of Microbiology of the Rutgers University . As the path between his residence in New York and the headquarters of Rutgers University in New Brunswick became increasingly difficult with increasing age , he moved to the medical faculty of New York University as an adjunct professor of pathological immunology in 1964 , where he was until shortly before his Death was active. He continued to study bacterial polysaccharides at both Rutgers University and New York University.

Private and family life

Michael Heidelberger was married for the first time from June 1916. Four years later, his only son, Charles Heidelberger, was born, who later also became a chemist. After his wife died of cancer in 1946 , Michael Heidelberger married nine years later a violist and music teacher who lived in the same house as he. In 1977, he had to undergo heart surgery from which he fully recovered in a short time. Six years later, his son, who devoted himself to cancer research and developed the cancer drug 5-fluorouracil , died six years later ; his second wife succumbed to longstanding Alzheimer's disease in 1988 .

In addition to his academic work, Michael Heidelberger took part in various political peace initiatives . In 1958, for example, he was one of the signatories of an appeal by American scientists to the US government and the peoples of the world to stop nuclear weapon tests , initiated by the later Nobel Peace Prize laureate Linus Pauling . During his time at New York University in 1970 he was involved in student protests against American military actions in Cambodia . The following year, at the age of 83, he went on a trip around the world with his second wife ; Besides traveling, his hobbies included playing the clarinet , which he mastered at a professional level, and collecting stamps . Narrated are chamber music performances by Michael Heidelberger at various scientific meetings with colleagues such as Felix Michael Haurowitz , the piano played.

Between 1977 and 1981 Michael Heidelberger published his memoirs in a series of three autobiographical articles that appeared in various journals . He died of a stroke in his hometown in 1991 at the age of 103 and was still working in the laboratory a few weeks earlier. With his death he left an unfinished manuscript for a scientific publication on which he had worked for the last two years of his life.

Scientific work

Working in the field of chemistry

Structural formula of the chemotherapeutically active substance tryparsamide, which Michael Heidelberger helped develop during his time at the Rockefeller Institute

In the first phase of Michael Heidelberger's career until around the mid-1920s, he worked as an employee of the Rockefeller Institute on various projects. Based on his training in organic chemistry, he initially focused on the synthesis of active ingredients for the treatment of infectious diseases such as syphilis and poliomyelitis . As part of this work, he contributed to the development of the substance tryparsamide , which was successfully used in the treatment of sleeping sickness , which is widespread in Africa and which was also used temporarily in the USA against neurosyphilis caused by Treponema pallidum . Together with Walter Jacobs, he published around 50 publications during this time, including in specialist journals such as the Journal of Biological Chemistry and the Proceedings of the National Academy of Sciences . In addition, together with Walter Jacobs, he succeeded in reproducing the synthesis of arsphenamine , a substance for the treatment of syphilis , developed in Paul Ehrlich's laboratory at the beginning of the 20th century . Further work from this period concerned studies of cardiac glycosides and quinine derivatives as well as chemical analysis . In 1923 a laboratory manual for organic chemistry was published.

Biochemical Studies

Schematic representation of the crystal structure of hemoglobin
Crystal structure of hemoglobin

After the First World War, Michael Heidelberger began to deal with biochemical issues such as the investigation of the properties of hemoglobin and its ability to bind oxygen . He devoted himself in particular to the representation of large amounts of the oxy form of hemoglobin in crystallized form for studies on the oxygen-hemoglobin balance. He also performed serological tests for his colleagues at the Rockefeller Institute. As part of his collaboration with Oswald Avery, Michael Heidelberger demonstrated that a soluble substance isolated by Avery and his colleagues from the shell of Pneumococcus cells, which had proven to be essential for the virulence of the bacteria, was free of nitrogen after purification .

In this way, he was able to prove that the substance was a carbohydrate and not a protein, as expected by the scientists involved. It was shown for the first time that polysaccharides act as antigens and can trigger the production of specific antibodies . With subsequent investigations on gum arabic , he also proved that comparable immunologically active carbohydrates are found in higher plants as well as bacteria . In addition, together with Oswald Avery, he was able to demonstrate that the bacterial capsular polysaccharides with antiserum , which was obtained from the blood of test animals after the injection of Pneumococcus cells , led to a reaction known as precipitation . This work shaped his lifelong interest in immunochemical issues.

Contributions to immunology

Photo of bacteria with polysaccharide capsule
Streptococcus pneumoniae with polysaccharide capsule, which is visible due to swelling after the addition of specific antisera

After moving to Columbia University and the Presbyterian Hospital, Michael Heidelberger established his own working group, which, however, rarely had more than two employees, usually a post-doctoral student and a technical assistant . In the years that followed, the research of the chemical and immunological properties of capsular polysaccharides became the central subject of his scientific interest. This work concerned in particular their isolation and purification as well as the elucidation of their structure through serological and chemical studies. By using different antisera, Michael Heidelberger demonstrated that a large number of immunologically specific polysaccharides exist in different types of bacteria. On the other hand, influenced by his previous work with Karl Landsteiner and Oswald Avery, he dealt with the elucidation of the nature of antigens and antibodies, whereby he combined methods of analytical chemistry with immunological research. Between 1929 and 1935 he described the methodological principles and a quantitative theory of the precipitin reaction in several publications.

A year later he was able to show that precipitation and agglutination are based on the same properties of an antiserum and not, as other immunologists suspect, two different forms of antibodies called “precipitins” and “agglutinins”. Building on his work on the precipitin reaction, he succeeded in a series of studies between 1936 and 1938 to prove that antibodies are proteins. Together with his colleague Elvin Kabat, he also found out through electrophoresis and ultracentrifugation that antibodies correspond to the gamma fraction of the globulins present in the serum . Based on the determination of the molecular mass and the sedimentation rate , they were also able to differentiate between two different types of antibodies, which at that time were named 7S and 19S and later became known as the immunoglobulin classes IgG and IgM . Furthermore, through further studies, they were able to improve the accuracy of the precipitin reaction and show that the agglutination of bacteria with antiserum was a precipitin reaction on the surface of the bacterial cells.

Around 20 publications by Michael Heidelberger - some together with Manfred M. Mayer - also concerned studies of the complement system and its effect on bacteria and on antigen-antibody complexes. Together with immunologists from Germany, he demonstrated, among other things, that the complement is a matter of various proteins in the blood plasma and not, as Jules Bordet postulated, a temporary colloidal state of the serum. Among other things, this confirmed earlier ideas by Paul Ehrlich .

reception

Life's work

Excerpt from a publication by Michael Heidelberger
A review ( Ann. Rev. Biochem. , 1935) by Michael Heidelberger on immunochemistry, a field that he co-founded and fundamentally influenced through his work

With the results of his research, Michael Heidelberger made a decisive contribution to the introduction of various bioanalytical methods based on the specific antigen-antibody reaction into research and clinical diagnostics . He played an important role in the development of immunology from a predominantly descriptive science to one that works with precise quantitative methods and in the establishment of immunochemistry as a new sub-discipline of immunology. The techniques he developed, in particular the precipitin reaction, and immunochemical methods derived from it, such as enzyme-linked immunosorbent assays and radioimmunoassays, enabled the identification, structure elucidation and quantitative measurement of proteins and polysaccharides with a degree of standardization , sensitivity and specificity that was previously not remotely achievable with any other method.

By proving that antibodies are proteins, he solved one of the most important questions in immunology of the time in the 1930s, which fundamentally changed the understanding of antibodies. This work led immunology away from the view that the reactions triggered by antisera were purely physical serum properties, which up to this point were referred to as the "antibody function" of the serum. Instead, the results of Michael Heidelberger's research led to the realization that antibodies are chemically defined molecules whose properties and interactions with antigens could be investigated and measured biochemically and molecularly. In the field of clinical immunology, his studies made significant contributions to the use of bacterial polysaccharides for vaccination against pneumococcal diseases, to investigate the effectiveness of immunizations and to elucidate the mechanisms of allergic reactions .

Due to his exceptionally long life, Michael Heidelberger was the last of the scientists since the death of Jules Bordet who marked the beginning of modern immunology with their research between 1950 and 1960. He published a total of 365  scientific publications , around 100 of them after his retirement in 1956. More than seven decades passed between his first publication in 1909 and the last in 1985. With this he published essays in every decade of the 20th century with the exception of the 1990s, an achievement that is considered unique in the history of science.

Awards

Michael Heidelberger's scientific achievements have been recognized in the United States and in other countries through high-level academic and government honors. Between 1947 and 1977 he received honorary doctorates from 15 different universities in Europe and the USA . In addition, he was admitted to the National Academy of Sciences (1942), the Royal Danish Academy of Sciences (1957), the Accademia Nazionale dei Lincei (1963), the American Philosophical Society (1968), the American Academy of Arts and Sciences (1972 ) and the Royal Society (1975) as well as being an honorary member of various national and international chemical, immunological and microbiological societies. Michael and Charles Heidelberger were among the few father-son couples who were members of the National Academy of Sciences together during their lifetime.

The prizes that he received included the Albert Lasker Award for Basic Medical Research (1953), the Emil von Behring Prize (1954), the National Medal of Science (1967), the Louisa-Gross- Horwitz Prize (1977), the Claude S. Hudson Award (1978) and the Albert Lasker Award for Clinical Medical Research (1978). He is one of the six scientists to date who have been honored twice by the Lasker Foundation . He was also awarded the Officer's Cross of the Belgian Order of Leopold II in 1953 and was appointed officer of the French Legion of Honor in 1966 , which had already awarded him the Knight's Cross in 1949 . Admission to the Legion of Honor, whose insignia he always wore on the lapel of his jacket, he attached particular importance to membership in the Royal Society. The Heidelberger-Kabat Distinguished Lectureship in Immunology at Columbia University, which has been awarded annually since 2001, is named after Michael Heidelberger .

Between 1937 and 1962 Michael Heidelberger was nominated 23 times for a Nobel Prize, 3 times for chemistry, 20 times for medicine.

Works (selection)

  • An Advanced Laboratory Manual of Organic Chemistry. New York 1923
  • Relation of Proteins to Immunity. In: Carl LA Schmidt (Ed.) The Chemistry of the Amino Acids. Springfield IL 1938, pp. 953-974
  • Recent Chemical Trends in the Study of Immunity. In: Maurice B. Visscher (Ed.): Chemistry and Medicine. Minneapolis 1940, pp. 139-156
  • Immunochemistry. In: David E. Green (Ed.): Currents in Biochemical Research. New York, 1946, pp. 453-460
  • Immunochemistry of Antigens and Antibodies. In: Robert A. Cooke (Ed.): Allergy in Theory and Practice. Philadelphia 1947, pp. 81-99
  • Lectures in Immunochemistry. New York 1956
  • Immunochemical Approaches to Problems in Microbiology. New Brunswick 1961 (as Associate Editor)
  • Perspectives in the Biochemistry of Large Molecules. New York 1962 (as editor)
  • Karl Landsteiner. June 14, 1868 - June 26, 1943. In: Biographical Memoirs. Volume 40. Washington DC 1969, pp. 176-210
  • Immunochemistry of Bacterial Polysaccharides. In: George Kwapinski (Ed.), Eugene D. Day (Ed.): Research in Immunochemistry and Immunobiology. Volume 3. Baltimore 1973, pp. 1-40

Individual evidence

  1. ^ A b c d e Elvin A. Kabat: Michael Heidelberger April 29, 1888 - June 25, 1991. In: Journal of Immunology. 148 (1 )/1992. American Association of Immunologists , pp. 301-307 (specifically p. 301), ISSN  0022-1767 , PMID 1727875
  2. ^ A b Maclyn McCarty in: Proceedings of the American Philosophical Society. 137 (3 )/1993. P. 432 (see literature)
  3. a b c Julius M. Cruse: A Centenary Tribute. Michael Heidelberger and the Metamorphosis of Immunologic Science. In: Journal of Immunology. 140 (9) / 1988. American Association of Immunologists , pp. 2861-2863, ISSN  0022-1767 , PMID 3283240
  4. ^ Maurice Stacey in: Biographical Memoirs of Fellows of the Royal Society. 39/1994. P. 179 (see literature)
  5. ^ A b Elvin A. Kabat: Michael Heidelberger April 29, 1888 - June 25, 1991. In: Journal of Immunology. 148 (1 )/1992. American Association of Immunologists , pp. 301-307 (specifically p. 302), ISSN  0022-1767 , PMID 1727875
  6. a b c Maurice Stacey in: Biographical Memoirs of Fellows of the Royal Society. 39/1994. P. 180 (see literature)
  7. ^ Herman N. Eisen in: Biographical Memoirs. 80/2001, p. 125 (see literature)
  8. ^ Herman N. Eisen in: Biographical Memoirs. 80/2001, p. 128 (see literature)
  9. ^ Maurice Stacey in: Biographical Memoirs of Fellows of the Royal Society. 39/1994. P. 195 (see literature)
  10. a b c Maurice Stacey in: Biographical Memoirs of Fellows of the Royal Society. 39/1994. P. 182 (see literature)
  11. a b c d e Maurice Stacey in: Biographical Memoirs of Fellows of the Royal Society. 39/1994. P. 183 (see literature)
  12. ^ Elvin A. Kabat: Michael Heidelberger April 29, 1888 - June 25, 1991. In: Journal of Immunology. 148 (1 )/1992. American Association of Immunologists , pp. 301-307 (specifically p. 306), ISSN  0022-1767 , PMID 1727875
  13. ^ A b c Maclyn McCarty in: Proceedings of the American Philosophical Society. 137 (3 )/1993. P. 436 (see literature)
  14. a b c d Maurice Stacey in: Biographical Memoirs of Fellows of the Royal Society. 39/1994. P. 190 (see literature)
  15. ^ Maurice Stacey in: Biographical Memoirs of Fellows of the Royal Society. 39/1994. P. 189 (see literature)
  16. ^ Elvin A. Kabat: Michael Heidelberger April 29, 1888 - June 25, 1991. In: Journal of Immunology. 148 (1 )/1992. American Association of Immunologists , pp. 301-307 (specifically p. 303), ISSN  0022-1767 , PMID 1727875
  17. Excerpts from "US Signatures to the Appeal by American Scientists to the Governments and People of the World." January 15, 1958 (accessed April 18, 2011)
  18. ^ A b Joan Cook: Michael Heidelberger Dies at 103; A Leader in Modern Immunology Obituary in: The New York Times . Published June 27, 1991
  19. ^ Herman N. Eisen in: Biographical Memoirs. 80/2001, p. 135 (see literature)
  20. ^ Michael Heidelberger: Reminiscences. In: Annual Review of Microbiology. 37/1977, pp. 1-12 (part 1); Annual Review of Biochemistry . 48/1979, pp. 1-21 (part 2); Perspectives in Biology and Medicine 24/1981, pp. 619–636 (Part 3)
  21. ^ Maclyn McCarty in: Proceedings of the American Philosophical Society. 137 (3 )/1993. P. 434 (see literature)
  22. ^ Elvin A. Kabat: Michael Heidelberger - active at 100. In: The FASEB Journal . 2 (7) / 1988. Federation of American Societies for Experimental Biology, pp. 2233/2234, ISSN  0892-6638 , PMID 3280377
  23. ^ A b Maurice Stacey in: Biographical Memoirs of Fellows of the Royal Society. 39/1994. P. 191 (see literature)
  24. ^ A b Maurice Stacey in: Biographical Memoirs of Fellows of the Royal Society. 39/1994. P. 181 (see literature)
  25. ^ Maclyn McCarty in: Proceedings of the American Philosophical Society. 137 (3 )/1993. P. 435 (see literature)
  26. ^ Maurice Stacey in: Biographical Memoirs of Fellows of the Royal Society. 39/1994. P. 192 (see literature)
  27. ^ Maurice Stacey in: Biographical Memoirs of Fellows of the Royal Society. 39/1994. P. 194 (see literature)
  28. ^ Ross Kessel: Obituary: Michael Heidelberger, April 29, 1888 - June 15, 1991. In: Immunology. 74 (2 )/1991. British Society for Immunology, pp. 365/366, ISSN  0019-2805
  29. ^ Herman N. Eisen in: Biographical Memoirs. 80/2001, p. 130 (see literature)
  30. ^ Otto Westphal: Michael Heidelberger. On the Occasion of his 90th Birthday on April 29, 1978. In: European Journal of Immunology. 8 (4) / 1978. European Federation of Immunological Societies, pp. 225-227, ISSN  0014-2980 , PMID 78850 .
  31. ^ A b Heather L. Van Epps: Michael Heidelberger and the Demystification of Antibodies. In: Journal of Experimental Medicine. 203 (1) / 2006. Rockefeller University Press, p. 5, ISSN  0022-1007 , PMID 16523537 , doi: 10.1084 / jem.2031fta .
  32. a b Julius M. Cruse: Michael Heidelberger (1888-1991): Transition from Life to Legend. In: Immunologic Research. 11 (1 )/1992. Humana Press, pp. 1-2, ISSN  0257-277X , PMID 3283240 .
  33. ^ Maurice Stacey in: Biographical Memoirs of Fellows of the Royal Society. 39/1994. Pp. 194/195 (see literature)
  34. ^ Maurice Stacey in: Biographical Memoirs of Fellows of the Royal Society. 39/1994. P. 196 (see literature)
  35. Columbia University - Department of Microbiology & Immunology: Heidelberger-Kabat Distinguished Lecture in Immunology (accessed March 20, 2010)
  36. ^ Nomination Database. In: nobelprize.org. April 17, 2015, accessed April 17, 2015 .

literature

  • Maurice Stacey: Michael Heidelberger. April 29, 1888 - June 25, 1991. In: Biographical Memoirs of Fellows of the Royal Society. 39/1994. The Royal Society, pp. 179-197, ISSN  0080-4606 , PMID 11639904 (with picture and bibliography).
  • Maclyn McCarty: Michael Heidelberger (April 29, 1888 - June 25, 1991). In: Proceedings of the American Philosophical Society. 137 (3 )/1993. American Philosophical Society, pp. 432-437 ISSN  0003-049X (with picture).
  • Herman N. Eisen: Michael Heidelberger. April 29, 1888 - June 25, 1991. In: Biographical Memoirs. Volume 80. National Academy of Sciences, Washington DC 2001, ISBN 0-309-08281-1 , pp. 122-141, PMID 15202469 (with picture and selected bibliography).

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