Microbe Hunters Revisited Paul de Kruif and the

Microbe Hunters Revisited Paul de Kruif and the Beginning of Popular Science Writing Stephen B. Greenberg, MD, MACP Dean of Medical Education, Baylor College of Medicine

Leeuwenhoek First of the Microbe Hunters Two hundred and fifty years ago an obscure man named Leeuwenhoek looked for the first time into a mysterious new world peopled with a thousand different kinds of tiny beings, many of them more important to mankind than any continent or archipelago. Chapter 1, Paragraph 1, Microbe Hunters, Paul de Kruif

Leeuwenhoek First of the Microbe Hunters Leeuwenhoek, unsung and scarce remembered, is now almost as unknown as his strange little animals and plants were at the time he discovered them. This is the story of Leeuwenhoek, the first of the microbe hunters. It is the tale of the bold and persistent and curious explorers and fighters of death who came after him. It is the plain history of their tireless peerings into this new fantastic world. They have tried to chart it, these microbe hunters and death fighters. So trying they have groped and fumbled and made mistakes and roused vain hopes. Some of them who were too bold have died – done to death by the immensely small assassins they were studying – and these have passed to an obscure small glory. Chapter 1, Paragraph 2, Microbe Hunters, Paul de Kruif

Paul de Kruif (1890 – 1971) • Born Zeeland, Michigan • Married Mary Fisher • Ph. D student of Fredric Novy – 1916 • “The Primary Toxicity of Normal Serum” JID (1917) • Pancho Villa expedition • WWI – Hygienic Corps – France • Worked on anti - toxin for gas gangrene

Scientific Blood Lines Emile Roux { Robert Koch Frederick Novy Paul de Kruif

Paul de Kruif • Worked at Pasteur Institute and met Emile Roux, Maurice Nicolle, Felix d’Herelle, and Hans Zimser • Returned to Novy and studied blood – dissolving toxin of Streptococcus bacillus • 1920 – Fell in love with lab technician Rhea Barbarin and divorced his wife Photo from Chernin E. Paul de Kruif’s Microbe Hunters and an Outraged Ronald Ross. Reviews of Infectious Diseases May – June 1988; 10 (3): 661 - 7.

Simon Flexner • Rockefeller Institute • Research on respiratory infections in rabbits • Asked de Kruif to resign in 1922 after writing scathing portrait of Rockefeller in “Our Medicine Men”

Henry Louis Mencken • Gave advice about writing • Took personal interest in de Kruif • Introduced him to Morris Fishbein (JAMA editor)

Paul de Kruif and Sinclair Lewis Morris Fishbein, MD Sinclair Lewis

Arrowsmith Jacques Loeb Frederick Novy + Dr. Max Gottlieb =

Covers of an American and Spanish edition of the Book From Summers WC. Microbe Hunters Revisited. Internatl Mircobiol 1998; 1: 65 -8.

Table of Contents Microbe Hunters by Paul de Kruif 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. Leeuwenhoek: First of the Microbe Hunters Spallanzani: Microbes Must Have Parents! Pasteur: Microbes are a Menace! Koch: The Death Fighter Pasteur: And the Mad Dog Roux and Behring: Massacre the Guinea Pigs Metchnikoff: The Nice Phagocytes Theobald Smith: Ticks and Texas Fever Bruce: Trail of the Tsetse Ross vs. Grassi: Malaria Walter Reed: In the Interest of Science – and for Humanity! 12. Paul Ehrlich: The Magic Bullet

Malaria vs. Sir Ronald Ross Giovanni Battista Grassi From Chernin E. Paul de Kruif’s Microbe Hunters and an Outraged Ronald Ross. Reviews of Infectious Diseases May – June 1988; 10 (3): 661 - 7.

Ronald Ross Grenada Grenadines, 1995 (1857 – 1932) • Born in India • Joined Indian Medical Service • Studied malaria in birds o Described oocysts of the malaria parasite in the walls of the stomach • “Grey, dappled winged mosquito” • Won Nobel Prize in 1902 Shampo MA and Kyle RA. The History of Malaria on Stamps. In Minnesota Medicine. Retrieved January 22, 2012 from http: //www. minnesotamedicine. com.

Ronald Ross’ Notebook Ross’ notebook where he first described pigmented malaria parasites in mosquitoes

Giovanni Battista Grassi Italy, 1955 (1854 – 1925) • Graduated from Pavia • Wanted to be zoologist • Became Professor of Zoology at Catania • Studied malaria in birds in Catania • 1890 – published on malarial cycle in different species of birds • Professor of Comparative Anatomy in Rome in 1895 • Expert on life cycle of eels • Did not win Nobel Prize Shampo MA and Kyle RA. The History of Malaria on Stamps. In Minnesota Medicine. Retrieved January 22, 2012 from http: //www. minnesotamedicine. com.

Giovanni Battista Grassi • On the basis of the epidemiology of malaria and the distribution of mosquitoes present in the malarial zones, he focused his investigations on three species suspected of malarial transmission, Anopheles claviger two and Culexspecies and he communicated this result to the Lincei Academy on September 19, 1898. • On November 6, 1898, Grassi announced to the Lincei Academy that, with two colleagues, Drs. Bignami and Bastianelli, he had infected a volunteer by exposing him to the bite of these three mosquito species. • On November 28, 1898, a formal note was sent to the academy and read in the academic session of December 4, 1898, where it was announced that a healthy man in a non – malarial zone had contracted tertian malaria after being bitten by an experimentally infected Anopheles claviger. • The experimental phase ended on December 22 with a communication to the Lincei Academy that described the entire development cycle of the plasmodium in the body of Anopheles claviger stated that it corresponded and to what Ross had described for Proteosoma in Culex pipiens in the malarial cycle of birds. From Capanna E. Grassi versus Rossi: Who Solved the Riddle of Malaria? Int Microbiol. 2006 March; 9(1): 69 - 74.

Clifford Dobell (1886– 1949) was a highly respected researcher working at the National Institute of Medical Research, Hampstead, and since 1918 a Fellow of the Royal Society. He had written The. Amoebae Livingin Man(1919) and The. Intestinal Protozoa Man (1921). Dobell was fascinated by of the discoveries of the seventeenth-century Dutchman Antony van Leeuwenhoek, who had described various “little animals” with the help of his self-designed microscopes. Dobell put his notes on van Leeuwenhoek at De Kruif's disposition for the writing of an essay that would become the first chapter of Microbe Hunters. From Verhave JP. Clifford Dobell and the Making of Paul de Kruif’s Microbe Hunters. Medical History. 2010 October ; 54: 529 -36.

Clifford Dobell “In one evening I could tell you more about Ross, Manson, Grassi, and everything else, than you could dig out for yourself in one year in N. Y. , U. S. A. And I could tell it to you accurately and fully, from my own completely biased standpoint—so that you would only have to go home and type it all out, ready for press. Well, if you won't come, I must send you some references. You must read: 1. “Memoirs” by Ronald Ross (London. John Murray. 1923) (Largely lies. ) 2. A letter—very moderate, for I retranslated and castigated it myself—in “Nature”, last year. 3. A short paper by Grassi in “Parasitology” Vol. XVI, No. 4, p. 355 December, 1924 (Translated by me. )” From Verhave JP. Clifford Dobell and the Making of Paul de Kruif’s Microbe Hunters. Medical History. 2010 October ; 54: 529 -36.

Clifford Dobell “This is a most complicated story, but the facts – very briefly – are as follows: 1. 2. 3. 4. Ross, instigated by Manson in England, and helped at every time by him, tried to discover how malaria is transmitted from man to man in India: and failed utterly. Ross then, —again egged on by Manson—tried to discover the mode of transmission of bird-malaria: and succeeded. Ross and Manson were unable to apply the knowledge gained from birds to the study of human malaria—because they knew next to nothing about zoology. Consequently, they couldn't do anything more—only guess (and guess wrong). Grassi and his collaborators in Italy had meantime got on the track of the true story regarding human malaria. They had already made some progress, when they heard of Ross's results with birds: and as Grassi was a good zoologist, he at once saw their significance, and went ahead and solved the problem. ” From Verhave JP. Clifford Dobell and the Making of Paul de Kruif’s Microbe Hunters. Medical History. 2010 October ; 54: 529 -36.

Clifford Dobell “Ross now claims that his work on birds solved the problem of human malaria. But it didn't, because even after he had finished the work on bird-malaria, he was hopelessly in the dark himself regarding the transmission of human malaria. So was Manson—whose ideas throughout were nearly all wrong. It was Grassi who discovered that malaria in man is transmitted by Anopheles, and who worked out the complete development of the human parasite in this mosquito. Ross is a very dirty dog. He told - that he “intended to live on the discoveries for the rest of his life. ” He has done so. Grassi is dirty, but not a dirty dog. He is a great zoologist, but savage or almost rabid when roused. I believe he is honest - after spending a long time corresponding with him and testing his statements in every way I can. He has always played the game with me, and I admire him as a worker, though not as an individual human being. ” From Verhave JP. Clifford Dobell and the Making of Paul de Kruif’s Microbe Hunters. Medical History. 2010 October ; 54: 529 -36.

Ross Grassi Intuitive Empirical Experimental Systematic Comparative Nobel Prize No Nobel Prize Dobell Paul de Kruif Microbe Hunters published Ross threatens lawsuit

Books by de Kruif Our Medicine Men (1922) Microbe Hunters (1926) Hunger Fighters (1928) Men Against Death (1932) Why Keep Them Alive (1937) Seven Iron Men (1937) The Fight for Life (1938) The Male Hormone (1945) Health is Wealth (1940) Life Among the Doctors (1949) Kaiser Wakes the Doctors (1950) A Man Against Insanity (1957) The Sweeping Wind (1962)

Paul de Kruif Medical Reporter/Activist • Reported on medical discoveries o Visited labs • Exposed malnutrition among U. S. poor • Campaign against tuberculosis (Detroit) and syphilis (Chicago) and poliomyelitis • Skirmishes with the AMA o Morris Fishbein • Apostle of Kaiser health plan and then attacked it • Alcoholics Anonymous supporter

Paul de Kruif • 200 magazine articles • Broadway Play o “Yellow Jack” • Movie “The Magic Bullet” • FDR and March of Dimes and National Foundation for Infinite Paralysis

Paul de Kruif The Challenge of Aging • The Male Hormone (1945) • Life among the Doctors (1949) • A Man Against Insanity (1958)

Paul de Kruif Medical Conscience of America • Love/hate relationship with doctors, researchers industrialists and politicians • Michigan State Senate and House of Representatives awarded his widow and third wife, Eleanor, a framed resolution • University of Michigan o Paul de Kruif Chair in Academic Pathology • Hope College o de Kruif writing prize • Buried in Zeeland From Verhave JP. Paul de Kruif: Medical Conscience of America. In: Swierenga RP, Nyenhuis JE, Kennedy N, eds. Dutch – American Arts and Letters in Historical Perspective. Holland, MI: Van Raalte Press; 2008: 191 – 202.

Microbe Hunters: Then and Now

The Next Generation of Microbe Hunters