Amboceptor

Microbiological, virological, bacteriological, immunological, medical, epidemiological, historical, anecdotal

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Wikipedia: Zinaida Ermolieva

Zinaida Vissarionovna Ermolieva (Russian: Зинаида Виссарионовна Ермольева; 15 October 1898 [O.S. 27 October] – 2 December 1974) was a Russian microbiologist and epidemiologist who led the Soviet effort to generate penicillin during the Second World War.


Biographyzinaida


Born on a farm in the Frolovo region, Ermolieva attended school in Novocherkassk and studied medicine at Don University in Rostov-on-Don (now part of Southern Federal University), graduating in 1921. Continuing to work at Don University’s bacteriological institute, she collaborated with Nina Kliueva on a study on encephalitis lethargica [1], before moving to Moscow in 1925. There she worked at the People’s Commissariat of Health, as head of microbiology at a biochemical institute [2] that would later be named for its founder Aleksey Nikolayevich Bakh [3]. Early in her career she was known for her work on characterizing lysozyme and employing it as an antimicrobial agent [4].

During the Second World War Ermolieva became famous for her role in the independent Soviet effort to extract penicillin from mold, using the species Penicillium crustosum [4] (rather than P. notatum, the species employed by Alexander Fleming and other British scientists). To test this penicillin treatment, she was one of many scientists to travel to Abkhazia and make use of the monkey colonies at Sukhumi’s Institute of Experimental Pathology and Therapy [5].

Ermolieva also led the efforts to control a cholera outbreak in Stalingrad, as part of which she spent six months in the besieged city, and was credited with creating a bacteriophage-based vaccine against Vibrio cholerae in addition to developing the new Soviet source for penicillin.

Now an eminent scientist and patriotic hero, she was awarded the State Stalin Prize and spent the rest of her career in Moscow, being named director of the All-Union Research Institute for Antibiotics in 1947, and chair of the department of microbiology at the Central Postgraduate Medical Institute in 1952. She was also a founder and editor of the Moscow-based journal Antibiotiki [4]. According to Soviet propaganda, Ermolieva chose to redirect the proceeds from her Stalin Prize into building fighter jets, one of which was inscribed with her name. She was also publicly recognized as a self-experimenter, reportedly swallowing 1.5 billion cells of a glowing blue Vibrio strain in order to show that it caused a cholera-like illness [7].

Ermolieva was named an Academician of the USSR Academy of Medical Sciences in 1965, and was named an Honored Scientist of the RSFSR in 1970 [8]. She received other state honors including the Order of the Red Banner of Labour, the Order of the Badge of Honour, and the Order of Lenin. Credited with over 500 scientific papers and as adviser for 34 doctoral theses in her career, Zinaida Vissarionovna Ermolieva died in Moscow in 1974.


Personal Life


Ermolieva was married twice, both times to fellow microbiologists. She was important in the efforts to free her ex-husband Lev Alexandrovich Zilber, who had been imprisoned in labor camps on suspicions of spying for Germany and misusing his research on tick-borne encephalitis virus and Japanese encephalitis virus [9]. Zilber was freed permanently in 1944 and later rehabilitated in the eyes of the Kremlin, receiving several of the same state honors as Ermolieva [10]. Her second husband, Aleksey Aleksandrovich Zakharov, was also a microbiologist who was denounced during the Second World War, and died in a prison hospital in 1940 [11].

She became a model for aspiring Soviet female scientists as the basis for protagonist Tatiana Vlasenkova in The Open Book, a trilogy of novels written between 1949 and 1956 by Veniamin Alexandrovich Kaverin, the brother of Lev Zilber [12]. The Open Book was adapted in feature film form in 1973 [13], and as a television series in 1977 [14]. She is also the basis for the character Anna Valerievna Dyachenko in the Russian TV series “Black Cats” (Чёрные кошки), set in postwar Rostov-on-Don [15].


References


1. Krementsov, Nikolai (2007). The Cure: A Story of Cancer and Politics from the Annals of the Cold War. Chicago: University of Chicago Press. p. 40. ISBN 9780226452845.

2. http://www.inbi.ras.ru/english/history.html

3. Kretovich, W.L. (1983), “A.N. Bach, Founder of Soviet School of Biochemistry”. in Semenza, G. Selected Topics in the History of Biochemistry: Personal Recollections (Comprehensive Biochemistry Vol. 35). Amsterdam: Elsevier Science Publishers. p. 346.

4.(pdf) S. Navashin (1975), Obituary of Prof. Zinaida Vissarionovna Ermolieva, The Journal of Antibiotics vol. XXVIII, no. 5, p. 399.

5. http://www.redorbit.com/news/science/1503065/renowned_science_facility_suffers_in_postsoviet_era/

7. Fiks, Arsen P (2003). Self-Experimenters: Sources for Study. Westport, CT: Praeger Publishers. p. 70.

8. “Zinaida Ermol’eva”. The Great Soviet Encyclopedia, 3rd edition (1970-1979).

9. Zlobin, V.I. et al. (2005). “Tick-Borne Encephalitis”. in Ebert, Ryan A. Progress in Encephalitis Research. New York: Nova Science Publishers, 2005. p.32. ISBN 1-59454-345-3.

10. “Lev Zil’ber”. The Great Soviet Encyclopedia, 3rd edition (1970-1979).

11. http://panov-a-w.narod.ru/stati/zilber.html

12. Eremeeva, Anna (2006). “The Woman Scientist in Soviet Artistic Discourse”. in Saurer, Edith; Lanzinger, Margareth; Frysak, Elisabeth. Women’s Movements: Networks and Debates in Post-Communist Countries in the 19th and 20th Centuries. Köln: Böhlau Verlag GmbH & Cie. p. 347. ISBN 9783412322052.

13. http://www.imdb.com/title/tt0170345/

14. http://www.imdb.com/title/tt0075554/

15. http://www.kino-teatr.ru/kino/movie/ros/104901/annot/

All facts not otherwise cited are from the Russian Wikipedia page on Zinaida Ermolieva, accessed via Google Translate on 24 August 2014.

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Two Octaves down

From looking up the basics of complement fixation, it turns out that it had other names. It was called complement deviation: instead of complement landing on cells and lysing them, its path was deviated to some other end. Just like complement fixation: before it can land on cells and lyse them, complement is fixed in place and stays in solution. This is all very straightforward.

It was also called “The Bordet-Gengou Reaction”. That sounds more interesting.

* * *

The best source for info on the early history of immunology is the book Immunology: Pasteur’s Heritage, edited by Pierre-André Cazenave and published in 1991 by Wiley. I have not read this book, but I will bet you $12 that it’s the best source for info on the early history of immunology. The passages available in Google Books are great.

Anyway, according to Wikipedia, complement itself was first called “alexin“, around 1890 by researcher Hans Ernst August Buchner, who observed that serum contained a substance that could lyse bacteria in the absence of cells. Richard Pfeiffer observed a similar phenomenon. Also around 1890, the word “antibody” (technically “Antikörper” because they were all publishing in German) was coined, by Paul Ehrlich whose laboratory was more focused on the interactions of individual molecules (in this case antibodies, which he saw could neutralize the harmful effects of toxins) than cells. All of these researchers were sort of rivals to the organization of Élie Metchnikoff at the Institut Pasteur in Paris, which was focused on the newly discovered phagocytic cells that he thought were responsible for all aspects of immune protection, more or less.

Jules Bordet

Jules Bordet

Belgian researcher Jules Bordet was an apprentice to Metchnikoff. And Octave Gengou was Bordet’s brother-in-law and close colleague. At some point in the late 1890s (I can’t tell which paper it was; all their papers were in Annales de l’Institut Pasteur, and most of them are just called “Recherches sur la coagulation du sang” with vague subtitles), Bordet showed that “alexine” was made up of two parts: a heat-stable part, which just bound up things like toxins and bacteria; and a part that could easily be destroyed by heat. Without this “heat-labile” element, the bacteria didn’t get lysed.

This led the Ehrlich school to divide its “Antikörper” concept into two parts: Amboceptor (heat-stable), and Komplement (heat-labile). Meanwhile the Bordet/Metchnikoff school divided it into substance sensibilitrice (sensitizing substance) and alexine (bacteria-lysing substance). Bordet showed that Amboceptor/sensibilitrice/antibody against a certain substance would only be present in the blood of people immunized with that substance; while just about any blood contained Komplement/alexine/complement which could lyse anything.

* * *

What about Gengou?

It looks like Bordet and Gengou start being paired together on these papers in 1901, which was also the year that Bordet was invited to be the director of the newly founded Institut Pasteur. Not the real one… the Institut Pasteur du Brabant in Brussels. Which was the only “Institut Pasteur” not to be an offshoot of the original one in France; this one was just called that because Madame Pasteur gave it her blessing. In the 1980s it moved away from the beautiful building on Parc Léopold, which now houses the Bavarian Representation to the EU (pdf), and was eventually merged with the Belgian government’s Scientific Institute of Public Health.

Jules Bordet and Octave Gengou are credited with discovering complement fixation. Earlier they had seen that the amboceptor/complement mixture that destroys bacteria (bacteriolysis) can also destroy red blood cells (hemolysis), provided the RBCs were from a different species or a different blood group (yes, they basically also discovered blood groups).

But if you take some serum with a lot of amboceptor and complement in it, and do a bacteriolysis… all the complement should get used up. Then you mix it with sheep red blood cells, and they don’t get lysed. What you just did was prove that the serum contained antibody against that particular bacteria. You can see how this would be useful. This is the Bordet-Gengou reaction.

* * *

What about the Nobel Prize?

Bordet and Gengou also discovered the bacterium that causes pertussis, which is now called Bordetella. That looks less silly than Gengouella, but the latter actually sounds better, to the cultured and discriminating ear, They also developed Bordet-Gengou agar, the ideal substance for growing Bordetella pertussis and distinguishing it from other small Gram-negative coccobacilli, In 1919, the first Nobel Prize ceremony in five years was held, and the prize in medicine and physiology was given to Bordet, aged 49, for achievements summarized most briefly as:

  • Complement
  • Complement fixation
  • Pertussis bacterium

Two of those are accomplishments shared with Gengou. And both of those were procedures named after both Bordet and Gengou: in addition to the Bordet-Gengou complement phenomenon, the isolation of Bordetella pertussis depended on culturing it on what is known as Bordet-Gengou agar). And yet, only one person got the prize.

octave-gengar

Octave Gengar

Granted, the prize had always been given to a single person: with two exceptions. One of them was in 1908, when it went to both Pasteur and Metchnikoff. Not to do that might have caused an outbreak of bad feelings to rival the Schism of 1054. I suppose Gengou would not mind the solitary recognition of his great collaborator.

Really, the biggest injustice is not the lack of a Nobel Prize, or the zero Google hits for the word “Gengouella”, but my inability to find any photos of him online.

* * *

The name “Octave” rang a bell. I don’t know if I’d heard of anyone by that name until this year. Who was the other one? Quickly the memory became clear: Octave Chanute.

octave-chanute

Octave Chanute

From flyingmachines.org:

Octave Alexandre Chanut*  , a native of France, was retired from a distinguished engineering career and living in Chicago, Illinois, when he began to pursue his life-long interest in aeronautics. His experiments with “gliding machines” began in 1896 and were conducted at Miller Beach and Dune Park, Indiana, on the southern shore of Lake Michigan.

Octave Chanute went on to be the main enthusiast for the Wright Brothers during their early aerial trials, encouraging them and supplying them with the latest aerial information. By 1900 Chanute had become the center point for various aerial experimenters in Europe and the U.S. His 1894 book “Progress in Flying Machines” was a landmark volume and was the book recommended to Wilbur Wright by the Smithsonian Institution in 1899.

One of the messages I got from the displays at the Wright Brothers National Memorial, on North Carolina’s Outer Banks, was that the brothers cared deeply about impressing Octave Chanute, whose correspondence served as a nexus for information exchange between different experimentalists in heavier-than-air flight. Chanute was unquestionably the nearest “giant” on whose shoulders they stood. But I had never heard of him until this year. Maybe you had.

Takeaway message: If your name is “Octave”, “Staff”, “Rest”, “Flat” or another musical term, your contributions may be overlooked by the eye of history. You may want to change your name. Make a note of it. But don’t make “Note” your name.

* * *

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