Stanley "Stan" Falkow (January 24, 1934 – May 5, 2018) was an American microbiologist and a professor of microbiology at Georgetown University, University of Washington, and Stanford University School of Medicine. Falkow is known as the father of the field of molecular microbial pathogenesis. He formulated molecular Koch's postulates, which have guided the study of the microbial determinants of infectious diseases since the late 1980s.Falkow S (1988). "Molecular Koch's postulates applied to microbial pathogenicity." Rev Infect Dis 10(Suppl 2):S274-S276. Falkow spent over 50 years uncovering molecular mechanisms of how bacteria cause disease and how to disarm them. Falkow also was one of the first scientists to investigate antimicrobial resistance, and presented his research extensively to scientific, government, and lay audiences explaining the spread of resistance from one organism to another, now known as horizontal gene transfer, and the implications of this phenomenon on our ability to combat infections in the future.
Early life and education Falkow was born into a Yiddish-speaking household in Albany, New York. His father was a shoe salesman and had immigrated from Soviet Kyiv, Ukraine.Sandeep Ravindran. Curious About Everything Stanford Alumni Magazine, September/October 2011, retrieved June 22 2018 His mother came from a family of Jewish immigrants from Poland. She "rented several of their bedrooms and later opened a corset shop". Falkow's family was working-class to poor as he described in his memoir. He was therefore a first-generation Jewish American. Falkow worked at a toy shop in order to collect enough money to buy a model microscope, as well as admitted to stealing textbooks, one a nurse's book on infectious diseases, in order to explore microbiology as a career path despite his family's financial situation.
Falkow attributed his early interest in microbiology to reading Microbe Hunters in 1943, when he was 9 years old, which he found at the public library after the family had moved to Newport, Rhode Island. The book is a dramatization of microbiological research written by American microbiologist Paul de Kruif. Because of poor grades until his senior year of high school, an adviser suggested military rather than college. Falkow described himself as an average student, and below average at mathematics, which he later rectified by working through workbooks of high school and college level mathematics later in his career, after earning his Ph.D., in order to analyze and design experiments. In his memoir, Falkow gives credit to his teachers and acknowledges the role that the systemic oppression of women in America in the 1940s–1950s played in his life, stating "I now understand that I was the beneficiary of the repression of women by our society. The best and brightest women in many communities were relegated to the one intellectual role deemed suitable for them. They became teachers and many poured their love of language, science, music and art into students like me."
Education and career Falkow enrolled in biology at the University of Maine, because of their microbiology department. During the summers he worked in pathology at the hospital in Newport, staining slides and assisting in autopsies. He graduated in 1955. Before he started graduate school at University of Michigan he developed extreme anxiety. He was later diagnosed with agoraphobia. He avoided movie theaters and crowded places between 1955 and 1983 and dropped out of his first attempt at graduate school because of recurring panic attacks. He returned to Rhode Island to live with his parents and work at the Newport Hospital as a technician, focusing on bacteriology and processing and examining patient samples. He re-enrolled in graduate school at Brown University and graduated with a PhD in 1961.
He finished his work for his Ph.D. thesis at the Walter Reed Army Institute of Research (WRAIR) in the Department of Bacterial Immunology. While at Walter Reed, he worked with African-American microbiologist Othello Washington. Washington was older and more experienced than Falkow, but was assigned to be Stan's technician. Upon meeting, Falkow and Washington decided it would be more appropriate and better for both men to work together as a team. The two men worked together on isolating mobile genetic elements and the transfer of genes between E. coli and Salmonella and published a paper together about Proteus species. Falkow also worked with Shigella species and contracted dysentery, which lead to hospitalization, after being exposed to infected monkey feces flung at his face by an infected monkey. Multiple times through his training and early career more senior scientists, some Nobel prize winners, recommended that Falkow focus more on mechanisms of gene expression and less on pathogens because "nobody cares about typhoid". Falkow remained interested in pathogens despite many warnings from his peers and supervisors that infectious diseases were not interesting and were becoming less frequent in wealthy countries and were therefore a diminishing field of study.
His early work in the 1960s focused on the genetic mechanisms, which enable bacteria to become resistant to antibiotics. He showed that organisms, such as Shigella, can possess DNA fragments called plasmids which exist apart from the bacterial chromosome, and that they carry specialized information for survival. Under selective pressure from antibiotics, one species of bacteria can pass its plasmids to another directly without mating, thereby preserving its own specialized survival genes.
In 1966, he joined Georgetown University School of Medicine as a professor of microbiology. He later moved to Seattle to join the faculty of the Department of Microbiology and Immunology at the University of Washington School of Medicine. Here he described how meningitis and gonorrhea organisms acquire plasmids to become resistant to penicillin and other antibiotics.
In the 1970s, Falkow shifted his focus to the infection process. During this period, he showed that a life-threatening diarrhea prevalent in many developing countries is caused by a sub-type of E. coli. He also co-authored (with Royston C. Clowes, Stanley N. Cohen, Roy Curtiss III, Naomi Datta and Richard Novick) a proposal for uniform nomenclature for bacterial plasmids.Richard P. Novick et al., "Uniform Nomenclature for Bacterial Plasmids: A Proposal", Bacteriol. Rev., March 1976, pp. 168–189.
In 1981, he was named chairman of the Department of Medical Microbiology at Stanford University School of Medicine, a position he held until 1985. While at Stanford, Falkow encouraged Esther Lederberg to continue directing the Stanford Plasmid Reference Center, an internationally used registry for plasmids, transposons and insertion sequences.See http://www.esthermlederberg.com/EImages/Archive/ArchiveIndex.html; click "Special Topics", "Plasmid Reference Center Funding Issues", then "Falkow")
Personal life and death Falkow was married to Rhoda Ostroff in January, 1958 with whom he had two daughters. They divorced in 1983.Harrison Smith Stanley Falkow, microbiologist who studied bacteria and the diseases they cause, dies at 84 Washington Post, 12 May 2018, retrieved 21 June 2018 In December, 1983, he married Lucy S. Tompkins.
Falkow and Tompkins met while he was a professor at Georgetown University, and she was a medical student who sought Falkow out to work in his lab. At first, Falkow denied the opportunity to Tompkins, claiming that he would not take female graduate students because he was not comfortable having a female student, which was common in the scientific field in the 1960s. Tompkins rebutted his misogyny firmly, and explicitly pointed out that he was discriminating against her based on her gender. Her argument forced Stan to reconsider his bias and he then allowed her to enter his laboratory as a trainee. For the remainder of his career Falkow continued to hire women trainees, and by the end of his career most of his trainees were female. Falkow later became an advocate and ally of gender equality in science and helped encourage many women to pursue scientific careers.
Falkow had on-going severe anxiety throughout his career. Due to his anxiety early in his career he avoided conferences, airplanes, and giving presentations in general due to the fact that he would shake and sweat noticeably during them. Falkow described his struggle with his mental health as an "uneasy truce" with his "demons" later on in his career as he learned various coping mechanisms. Because of his anxiety during public speaking, he often employed humor in his teaching and presentations to help cope with the tension of a silent audience, which also lead to most of the audience members finding his talks memorable and enjoyable. Falkow kept his condition a secret from his colleagues during his early career, only privately revealing to Arthur Saz, the chair of microbiology at Georgetown University School of Medicine, that he received and benefited from psychoanalysis treatment. Health insurance for mental health treatment was much better for military employees than academics at the time, and a major reason Falkow continued to work at the Walter Reed Army Institute of Research for as long as he did early in his career, but Falkow agreed to a job at Georgetown University because of this disclosure, upon which the chair privately organized Falkow's healthcare benefits to cover his psychoanalysis treatments.
In 2004 Falkow was diagnosed with myelodysplastic syndrome and given a prognosis of two years. He died on May 5, 2018, at the age of 84 at his home in Portola Valley, California, of myelodysplastic syndrome. His death was announced and lifetime achievements highlighted in obituaries in The New York Times, Washington Post, Nature, Science, in a press release from the Americain Society of Microbiology and in various international news sources.
Contributions
Molecular microbiology research Falkow has been referred to as the "father of molecular microbial pathogenesis", the study of how infectious microbes and host cells interact to cause disease at the molecular level.The Double Helix NFID to Honor Dr. Falkow Retrieved on July 4, 2007 Falkow adopted the perspective of viewing infection as a process that is ultimately dependent on both the infecting agent and the host. He discovered that infectious microbes employ genes that are activated only inside host cells. His work carries clinical applications, such as a new vaccine for whooping cough. From enteric pathogens to sexually transmitted diseases to respiratory infections, his influence has left virtually no field untouched.
Falkow and his first graduate student, Richard P. Silver, discovered that episomes (plasmids) are nicked into linear pieces of DNA and transported as linear DNA between two bacterial cells during conjugation. He then collaborated with Mexican scientists Emma Galindo and Jorge Olarte to investigate new forms of penicillin resistance in Shigella isolates from pediatric patients in Mexico City, which lead to the discovery of new forms of "R factors" - genes responsible for antimicrobial resistance. Falkow and trainee Joan Skerman Knapp identified a virulence factor on plasmids of E. coli found in human feces, demonstrating for the first time that the ability to cause disease may be transferable between bacteria.
Falkow was present at the famous Waikiki beach meeting in 1972 between Herb Boyer (who provided the restriction enzyme EcoRI) and Stanley Cohen (who provided the plasmid) that led to a plan to develop recombinant DNA technology. This led to the first cloning of a bacterial virulence factor, the heat stable toxin of E. coli, in a seminal 1976 paper with Magdalene Yh So, which heralded the application of molecular genetics to understanding gene transfer, and ultimately led to the creation of the field of synthetic biology.