[1] Falkow attributed his early interest in microbiology to reading Microbe Hunters in 1943, when he was 11 years old, which he found at the public library after the family had moved to Newport, Rhode Island.

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.

[4] He finished his work for his Ph.D. thesis at the Walter Reed Army Institute of Research (WRAIR) in the Department of Bacterial Immunology.

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.

[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".

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.

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.

[1] Falkow later became an advocate and ally of gender equality in science and helped encourage many women to pursue scientific careers.

[4] 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.

[10] His death was announced and lifetime achievements highlighted in obituaries in The New York Times,[11] Washington Post,[12] Nature,[13] Science,[9] in a press release from the Americain Society of Microbiology[14] and in various international news sources.

[citation needed] From enteric pathogens to sexually transmitted diseases to respiratory infections, his influence has left virtually no field untouched.

[19][1] 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 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 of Salmonella and Shigella in patient samples based on lysine metabolism,[22] the application of nucleic acid hybridization to distinguish different bacterial species,[23] the application of agarose gels to isolate plasmids of various sizes,[24] isolation and creation of different plasmid backbones now used as cloning vectors,[25] a method for identifying unculturable pathogens based on isolated 16S ribosomal RNA sequence,[26] an optimized version of GFP for flow 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.

[7] Falkow established ‘Molecular Koch’s postulates’ for defining virulence determinants,[2] which continues to influence thinking and experimental design in infectious disease research.

[32][1] Falkow and his student Vickers Herschfield investigated water sources in the D.C. area to find examples of plasmids containing antimicrobial resistance genes.

Unexpectedly, they found that the Potomac River and Rock 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.

[34] Falkow worked with the FDA of the United States throughout his career to advocate for the decrease of antimicrobial agents used in livestock feed.

[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.