Stanley Falkow | |
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| Born | (1934-01-24)January 24, 1934 |
| Died | May 5, 2018(2018-05-05) (aged 84) |
| Education | University of Maine Brown University |
| Occupation(s) | Technician,Newport Hospital (1956–1957) Scientist,Walter Reed Army Institute of Research (1961–1966) Professor,Georgetown University (1967–1972) Professor,University of Washington (1972–1981) Professor,Stanford University (1981–2018) |
| Known for | Antibiotic resistance and molecular microbiology research |
| Partner(s) | Rhoda Ostroff (m.1958–1983) Lucy S. Tompkins (m. 1983–2018) |
| Children | 2 |
| Awards | |
| Scientific career | |
| Thesis | An episomic element in a strain of Salmonella typhosa (1960) |
| Doctoral advisor | Charles ("Doc") Arthur Stuart, Brown University |
| Signature | |
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Stanley "Stan" Falkow (January 24, 1934 – May 5, 2018) was an American microbiologist and a professor ofmicrobiology atGeorgetown University,University of Washington, andStanford University School of Medicine. Falkow is known as the father of the field of molecular microbial pathogenesis.[1] He formulatedmolecular Koch's postulates, which have guided the study of the microbial determinants of infectious diseases since the late 1980s.[2] Falkow spent over 50 years uncovering molecular mechanisms of how bacteria cause disease and how to disarm them.[1] 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 ashorizontal gene transfer, and the implications of this phenomenon on our ability to combat infections in the future.[1]
Falkow was born into a Yiddish-speaking household inAlbany, New York. His father was a shoe salesman and had immigrated from SovietKyiv, Ukraine.[3] His mother came from a family of Jewish immigrants from Poland. She "rented several of their bedrooms and later opened a corset shop".[4] Falkow's family was working-class to poor as he described in his memoir.[1] 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.[1]
Falkow attributed his early interest in microbiology to readingMicrobe Hunters in 1943, when he was 11 years old, which he found at the public library after the family had moved toNewport, Rhode Island. The book is a dramatization of microbiological research written by American microbiologistPaul de Kruif.[5]Because of poor grades until his senior year of high school, an adviser suggested military rather than college.[4] 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.[1] 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."[1]
Falkow enrolled in biology at theUniversity 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.[4]Before he started graduate school atUniversity of Michigan he developed extreme anxiety. He was later diagnosed withagoraphobia. He avoided movie theaters and crowded places between 1955 and 1983[4] and dropped out of his first attempt at graduate school because of recurring panic attacks.[3][4] 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.[1] He re-enrolled in graduate school atBrown University and graduated with a PhD in 1961.[4]
He finished his work for his Ph.D. thesis at theWalter Reed Army Institute of Research (WRAIR) in the Department of Bacterial Immunology.[1] While at Walter Reed, he worked with African-American microbiologistOthello 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 isolatingmobile genetic elements and the transfer of genes betweenE. coli andSalmonella and published a paper together aboutProteus species.[1][6] Falkow also worked withShigella species and contracteddysentery, which lead to hospitalization, after being exposed to infected monkey feces flung at his face by an infected monkey.[1] 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".[1] 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.[1]
His early work in the 1960s focused on the genetic mechanisms, which enable bacteria to become resistant to antibiotics. He showed that organisms, such asShigella, can possess DNA fragments calledplasmids 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 joinedGeorgetown University School of Medicine as a professor of microbiology. He later moved toSeattle to join the faculty of the Department of Microbiology and Immunology at theUniversity of Washington School of Medicine. Here he described howmeningitis andgonorrhea organisms acquire plasmids to become resistant topenicillin and otherantibiotics.[1]
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 ofE. coli. He also co-authored (withRoyston C. Clowes,Stanley N. Cohen,Roy Curtiss III,Naomi Datta andRichard Novick) a proposal for uniform nomenclature for bacterial plasmids.[7]
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 encouragedEsther Lederberg to continue directing the StanfordPlasmid Reference Center, an internationally used registry for plasmids, transposons and insertion sequences.[8])
Falkow was married to Rhoda Ostroff in January, 1958 with whom he had two daughters. They divorced in 1983.[4] In December, 1983, he marriedLucy S. Tompkins.[4]
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.[1] Tompkins rebutted hismisogyny firmly, and explicitly pointed out that he was discriminating against her based on her gender.[1] Her argument forced Stan to reconsider his bias and he then allowed her to enter his laboratory as a trainee.[1] 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.[1] Falkow later became an advocate and ally ofgender equality in science and helped encourage many women to pursue scientific careers.[9]
Falkow had on-going severeanxiety 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.[1] Falkow described his struggle with hismental health as an "uneasy truce" with his "demons" later on in his career as he learned various coping mechanisms.[1] 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.[4] Falkow kept his condition a secret from his colleagues during his early career, only privately revealing to Arthur Saz, the chair of microbiology atGeorgetown University School of Medicine, that he received and benefited frompsychoanalysis treatment.[1]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 theWalter Reed Army Institute of Research for as long as he did early in his career, but Falkow agreed to a job atGeorgetown University because of this disclosure, upon which the chair privately organized Falkow's healthcare benefits to cover his psychoanalysis treatments.[1]
In 2004 Falkow was diagnosed withmyelodysplastic syndrome and given a prognosis of two years.[4] He died on May 5, 2018, at the age of 84 at his home inPortola Valley, California, ofmyelodysplastic syndrome.[10] His death was announced and lifetime achievements highlighted in obituaries inThe New York Times,[11]Washington Post,[12]Nature,[13]Science,[9] in a press release from theAmericain Society of Microbiology[14] and in various international news sources.
Falkow has been referred to as the "father of molecular microbialpathogenesis", the study of how infectiousmicrobes and host cells interact to cause disease at the molecular level.[15]Falkow adopted the perspective of viewing infection as a process that is ultimately dependent on both the infecting agent and the host.[1][16] He discovered that infectious microbes employgenes that are activated only inside host cells. His work carries clinical applications, such as a new vaccine forwhooping cough.[citation needed] From enteric pathogens to sexually transmitted diseases to respiratory infections, his influence has left virtually no field untouched.[17]
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 duringconjugation.[18] He then collaborated with Mexican scientistsEmma Galindo andJorge Olarte to investigate new forms of penicillin resistance inShigella isolates from pediatric patients in Mexico City, which lead to the discovery of new forms of "R factors" - genes responsible for antimicrobial resistance.[19][1] Falkow and traineeJoan Skerman Knapp identified a virulence factor on plasmids ofE. coli found in human feces, demonstrating for the first time that the ability to cause disease may be transferable between bacteria.[20]
Falkow was present at the famous Waikiki beach meeting in 1972 betweenHerb Boyer (who provided the restriction enzyme EcoRI) andStanley Cohen (who provided the plasmid) that led to a plan to developrecombinant DNA technology. This led to the first cloning of a bacterial virulence factor, the heat stabletoxin ofE. coli, in a seminal 1976 paper withMagdalene Yh So, which heralded the application of molecular genetics to understanding gene transfer, and ultimately led to the creation of the field ofsynthetic biology.
Falkow and his trainees developed many methods that moved biological research forward such as: a method for screening patient samples for enteric pathogens,[21] the identification ofSalmonella andShigella in patient samples based on lysinemetabolism,[22] the application ofnucleic acid hybridization to distinguish different bacterial species,[23] the application ofagarose gels to isolate plasmids of various sizes,[24] isolation and creation of different plasmid backbones now used ascloning vectors,[25] a method for identifying unculturable pathogens based on isolated16S ribosomal RNA sequence,[26] an optimized version ofGFP forflow cytometry applications,[27] and a fluorescence-based method for the detection of genes expressed by pathogens inside of host cells,[28] among many other techniques.
After studying the DNA content of many different pathogenic microbes, Falkow became one of the first scientists to suggest bacterial taxonomy should be based on DNA composition rather than phenotypic observations.[29][30]
Falkow and others created the universal nomenclature scheme forplasmids still in use today.[7]
Falkow established ‘Molecular Koch’s postulates’ for defining virulence determinants,[2] which continues to influence thinking and experimental design in infectious disease research.[17]
Falkow valued and enjoyed teaching as a fundamental part of scientific training and believed that all scientists have a duty to teach and train the next generation.[1] In all of his years of employment at academic institutions, he taught students in some capacity between medical, graduate, undergraduate courses and invited lectures for courses whenever he was able to.[1] In 2010, he recorded lectures on microbial pathogenesis for iBiology, and those videos are still publicly available on theiBiology website and onYouTube.[16] When Falkow became an emeritus Professor at Stanford University, he still taught students. Indeed, he co-taught withLucy Tompkins a class open to undergraduate and graduate students on the history of Infectious Disease.[31]
Falkow organized the first international symposium of invited speakers on antimicrobial resistance.[32][1]
Falkow and his studentVickers Herschfield investigated water sources in the D.C. area to find examples of plasmids containing antimicrobial resistance genes. Unexpectedly, they found that thePotomac River andRock Creek, considered "clean" water sources used for recreation at the time, were full of fecal waste and alerted many government offices about their findings, which were at first largely ignored.[1] In the summer of 1971, Falkow held a press conference warning D.C. citizens not to let their children play in the Potomac River, stating "one cup of Potomac River water is equivalent to a half gram of human feces".[1][33]
Falkow served on the first NIH Recombinant DNA committee to recommend policy guidelines for the use of recombinant DNA to the United States of America Congress.[1] Many of Falkow's publications are referenced in theRecombinant DNA Regulation Act of 1977.[34]
Falkow worked with theFDA of the United States throughout his career to advocate for the decrease of antimicrobial agents used in livestock feed.[1][35][36]
Falkow was elected President of theAmerican Society for Microbiology from July 1997 through June 1998. He was elected to the Institute of Medicine in 1997 and received theMaxwell Finland Award from the National Foundation of Infectious Diseases in 1999. He also received in 1999 an Honorary Doctor of Science,University of Guelph,Guelph,Ontario, and theUniversity of Maine Alumni Career Award. He has received honorary doctorates in Europe and the US. He received numerous awards for his achievements in science, including theBristol-Myers Squibb Award for Distinguished Achievement in Infectious Disease Research,[37] the Altemeier Medal from the Surgical Infectious Diseases Society of America, theHoward Taylor Ricketts Award Lecture at theUniversity of Chicago, and thePaul Ehrlich and Ludwig Darmstaedter Prize. In 2003, he received the Abbott Lifetime Achievement Award from theAmerican Society for Microbiology and theSelman A. Waksman Award in Microbiology from theNational Academy of Sciences.[38]He received theRobert Koch Award in 2000.[39]
Falkow was an elected member of theInstitute of Medicine, the National Academy of Sciences, and the National Academy of Arts and Sciences, an elected Fellow of the American Association for the Advancement of Science. He was also elected into the UK'sRoyal Society as a Foreign Member.[40]
In September 2008, Falkow was awarded theLasker Award for medical research.[41]
In May, 2016, Falkow was awarded by Barack Obama the National Medal of Science for his monumental contributions toward understanding how microbes cause disease and resist the effects of antibiotics, and for his inspiring mentorship that created the field of molecular microbial pathogenesis.[42]
Stanley Falkow is known for training many experts in the field of molecular microbiology who then became prominent professors and scientists all over the world, including;
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