as patients would ask why they were being denied curative treatment. other patients were pressured or compelled into the treatment without their own consent. cotton had his two sons' teeth extracted as preventive healthcare—although each later committed suicide. in the 1930s, however, focal infection fell from psychiatry as an explanation, cotton having died in 1933. criticism and decline (1930s–1950s) early skepticism addressing the eastern medical society in december 1918, new york city physician robert morris had explained that focal infection theory had drawn much interest but that understanding was incomplete, while the theory was earning disrepute through overzealousness of some advocates. morris called for facts and explanation from scientists before physicians continued investing so steeply in it, already triggering vigorous disputes and embittering divisions among clinicians as well as uncertainty among patients. in 1919, the american dental association's forerunner, the national dental association, held in new orleans its annual meeting, where c edmund kells, the originator and pioneer of dental x-ray, delivered a lecture, published in 1920 in the association's journal, largely discussing focal infection theory, which kells condemned as a "crime". kells stressed that x-ray technology is to improve dentistry, not to enhance the "mania of extracting devitalized teeth". kells urged dentists to reject physicians' prescriptions of tooth extractions. focal infection theory's elegance suggested simple application, but the surgical removals brought meager "cure" rate, occasional disease worsening, and inconsistent experimental results. still, the lack of controlled clinical trials, among present criticism, was normal at the time—except in new york city. around 1920, at henry cotton's claims of up to 85% success treating schizophrenia and manic depression, cotton's major critic was george kirby, director of the new york state psychiatric institute on ward's island. as colleagues of kirby, two researchers—bacteriologist nicolas kopeloff and psychiatrist clarence cheney—ventured from ward's island to trenton, new jersey, to investigate cotton's practice. research attacks in two controlled clinical trials with alternate allocation of patients, nicolas kopeloff, clarence cheney, and george kirby concluded cotton's psychiatric surgeries ineffective: those who improved were already so prognosed, and others improved without surgery. publishing two papers, the team presented the findings at the american psychiatric association's 1922 and 1923 annual meetings. at johns hopkins university, phyllis greenacre questioned most of cotton's data, and later helped steer american psychiatry into psychoanalysis. antipsychotic colectomy vanished except in trenton until cotton—who used publicity and word of mouth, kept the 30% death rate unpublicized, and passed a 1925 investigation by new jersey senate—died by heart attack in 1933. by 1927, weston price's researches had been criticized for allegedly "faulty bacterial technique". in the 1930s and 1940s, researchers and editors dismissed the studies of price and of edward rosenow as flawed by insufficient controls, by massive doses of bacteria, and by contamination of endontically treated teeth during extraction. in 1938, russell cecil and d murray angevine reported 200 cases of rheumatoid arthritis, but no consistent cures by tonsillectomies or tooth extractions. they commented, "focal infection is a splendid example of a plausible medical theory which is in danger of being converted by its enthusiastic supporters into the status of an accepted fact." newly a critic, cecil alleged that foci were "anything readily accessible to surgery". in 1939, e w fish published landmark findings that would revive endodontics. fish implanted bacteria into guinea pigs' jaws, and reported that four zones of reaction consequently developed. fish reported that the first zone was the zone of infection, whereas the other three zones—surrounding the zone of infection—revealed immune cells or other host cells but no bacteria. fish theorized that by removing the infectious nidus, dentists would permit recovery from the infection this reasoning and conclusion by fish became the basis for successful root-canal treatment. still, endodontic therapy of the era indeed posed substantial risk of failure, and fear of focal infection crucially motivated endontologists to develop new and improved technology and techniques. end of the focal era the review and "critical appraisal" by hobart a reimann and w paul havens, published in january 1940, was perhaps the most influential criticism of focal infection theory. recasting british surgeon william hunter's landmark pronouncements of 30 years earlier as widely misinterpreted, they summarized that "the removal of infectious dental focal infections in the hope of influencing remote or general symptoms of disease must still be regarded as an experimental procedure not devoid of hazard". by 1940, louis i grossman's textbook root canal therapy flatly rejected the methods and conclusions made earlier by weston price and especially by edward rosenow. amid improvements in endodontics and medicine, including release of sulfa drugs and antibiotics, a backlash to the "orgy" of tooth extractions and tonsillectomies ensued. k a easlick's 1951 review in the journal of the american dental association notes, "many authorities who formerly felt that focal infection was an important etiologic factor in systemic disease have become skeptical and now recommend less radical procedures in the treatment of such disorders". a 1952 editorial in journal of the american medical association tolled the era's end by stating that "many patients with diseases presumably caused by foci of infection have not been relieved of their symptoms by removal of the foci", that "many patients with these same systemic diseases have no evident focus of infection", and that "foci of infection are as common in apparently healthy persons as in those with disease". although some support extended into the late 1950s, focal infection vanished as the primary explanation of chronic, systemic diseases, and the theory was generally abandoned in the 1950s. revival and evolution (1990s–2010s) despite the general theory's demise, focal infection remained a formal, if rare, diagnosis, as in idiopathic scrotal gangrene and angioneurotic edema. meanwhile, by way of continuing case reports claiming cures of chronic diseases like arthritis after extraction of infected or root-filled teeth, and despite lack of scientific evidence, "dental focal infection theory never died". in fact, severe endodontic disease resembles classic focal infection theory. in 1986, it was noted that, "in spite of a decline in recognition of the focal-infection theory, the association of decayed teeth with systemic disease is taken very seriously". eventually, the theory of focal infection drew reconsideration. conversely, attribution of endocarditis to dentistry has entered doubt via case-control study, as the species usually involved is present throughout the human body. stealth pathogens with the 1950s introduction of antibiotics, attempts to explain unexplained diseases via bacterial etiology seemed all the more unlikely. by the 1970s, however, it was established that antibiotics could trigger bacteria switch to their l phase. eluding detection by traditional methods of medical microbiology, bacterial l forms and the similar mycoplasma—and, later, viruses—became the entities expected in the theory of focal infection. yet until the 1980s, such researchers were scarce, largely due to scarce funding for such investigations. despite the limited funding, research established that l forms can adhere to red blood cells and thereby disseminate from foci within internal organs such as the spleen, or from oral tissues and the intestines, especially during dysbiosis. perhaps some of weston price's identified "toxins" in endodontically treated teeth were l forms, thought nonexistent by bacteriologists of his time and widely overlooked into the 21st century. apparently, dental infections, including by uncultured or cryptic microorganisms, contribute to systemic diseases. periodontal medicine at the 1990s' emergence of epidemiological associations between dental infections and systemic diseases, american dentistry scholars have been cautious, some seeking successful intervention to confirm causality. some american sources emphasized epidemiology's inability to determine causality, categorized the phenomena as progressive invasion of local tissues, and distinguished that from focal infection theory—which they assert was evaluated and disproved by the 1940s. others have found focal infection theory's scientific evidence still slim, but have conceded that evolving science might establish it. yet select american authors affirm the return of a modest theory of focal infection. european sources find it more certain that dental infections drive systemic diseases, at least by driving systemic inflammation, and probably, among other immunologic mechanisms, by molecular mimicry resulting in antigenic crossreaction with host biomolecules, while some seemingly find progressive invasion of local tissues compatible with focal infection theory. acknowledging that beyond epidemiological associations, successful intervention is needed to establish causality, they emphasize that biological explanation is needed atop both, and the biological aspect is thoroughly established already, such that general healthcare, as for cardiovascular disease, must address prevalent periodontal disease, a stance matched in indian literature. thus, there has emerged the concept periodontal medicine. amid continuing research interest, indian textbooks find focal infection theory established, if in more modest form than originally. akshata et al have attacked the stigma and posed focal infection theory as a correct theory earlier misapplied and thereby discredited yet later refined as knowledge grew over time. in a paper winning an indian prize, they clarify "that the oral cavity can act as the site of origin for dissemination of pathogenic organisms to distant body sites, especially in immunocompromised hosts", especially those "suffering from malignancies, diabetes, rheumatoid arthritis", or "undergoing other immunosuppressive treatment", and that "uncontrolled advanced periodontitis" "presents a substantial infectious burden for the entire body by releasing bacteria, bacterial toxins, and other inflammatory mediators into the bloodstream that then affect the other parts of the body", this altogether "a paradigm shift in thinking about the directionality of oral and systemic associations". dental controversies during the 1980s, dentist hal huggins, sparking severe controversy, spawned biological dentistry, which claims that conventional tooth extraction routinely leaves within the tooth socket the periodontal ligament that often becomes gangrenous, then, forming a jawbone cavitation seeping infectious and toxic material. sometimes forming elsewhere in bones after injury or ischemia, jawbone cavitations are recognized as foci also in osteopathy and in alternative medicine, but conventional dentists generally conclude them nonexistent. although the international academy of oral medicine & toxicology claims that the scientific evidence establishing existence of jawbone cavitations is overwhelming and even published in textbooks, the diagnosis and related treatment remain controversial, and allegations of quackery persist. huggins and many biological dentists also espouse weston price's findings on endodontically treated teeth routinely being foci of infection, although these dentists have been accused of quackery. conventional belief is that microorganisms within inaccessible regions of a tooth's roots are rendered harmless once entrapped by the filling material, although little evidence supports this. a h rogers in 1976 and e h ehrmann in 1977 had dismissed any relation between endodontics and focal infection. at dentist george meinig's 1994 book, root canal cover-up, discussing researches of rosenow and of price, some dentistry scholars reasserted that the claims were evaluated and disproved by the 1940s. yet meinig was but one of at least three authors who in the early 1990s independently renewed the concern. boyd haley and curt pendergrass reporting finding especially high levels of bacterial toxins in root-filled teeth. although such possibility appears especially likely amid compromised immunity—as in individuals cirrhotic, asplenic, elderly, rheumatoid arthritic, or using steroid drugs—there remained a lack of carefully controlled studies definitely establishing adverse systemic effects. conversely, some if few studies have investigated effects of systemic disease on root-canal therapy's outcomes, which tend to worsen with poor glycemic control, perhaps via impaired immune response, a factor largely ignored until recently, but now recognized as important. still, even by 2010, "the potential association between systemic health and root canal therapy has been strongly disputed by dental governing bodies and there remains little evidence to substantiate the claims". the traditional root-filling material is gutta-percha, whereas a new material, biocalex, drew initial optimism even in alternative dentistry, but biocalex-filled teeth were later reported by boyd haley to likewise seep toxic byproducts of anaerobic bacterial metabolism. seeking to sterilize the tooth interior, some dentists, both alternative and conventional, have applied laser technology. although endodontic therapy can fail and eventually often does, dentistry scholars maintain that it can be performed without creating focal infections. and even by 2010, molecular methods had rendered no consensus reports of bacteremia traced to asymptomatic endodontic infection. in any event, the predominant view is that shunning endodonthic therapy or routinely extracting endodontically treated teeth to treat or prevent systemic diseases remains unscientific and misguided. footnotes see, for example, david schlossberg, ed, clinical infectious disease, 2nd edn (cambridge university press, 2015), and yomamoto t, "triggering role of focal infection...", in harabuchi y et al, eds, recent advances in tonsils and mucosal barriers of