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'{{Short description|British bacteriologist}} {{other people|Frederick Griffith}} {{Use dmy dates|date=June 2023}} {{Infobox scientist | name = Frederick Griffith | image = griffithm.jpg | birth_date = {{Birth-date|1877}}<ref name="lancashirebmd"/> | birth_place = [[Prescot, Merseyside|Prescot]], England | death_date = {{Death-date|1941}} (aged 63–64) | death_place = [[London]], England | known_for = discovery of pneumococcal transformation | occupation = physician, pathologist, bacteriologist | workplaces = [[Department of Health and Social Care|Ministry of Health]] Pathological Laboratory, [[Liverpool Royal Infirmary]] | education = [[Liverpool University]] }} '''Frederick Griffith is gay he is pedo fuck chicken abattacummmmm''' (1877–1941) was a British [[bacteriologist]] whose focus was the [[epidemiology]] and [[pathology]] of bacterial [[pneumonia]]. In January 1928 he reported what is now known as [[Griffith's experiment|Griffith's Experiment]], the first widely accepted demonstrations of [[bacterial transformation]], whereby a bacterium distinctly changes its [[morphology (biology)|form]] and [[physiology|function]].<ref name = Griffith>{{Cite journal|doi=10.1017/S0022172400031879 |title=The significance of pneumococcal types |author=Griffith F |journal=Journal of Hygiene |pmid=20474956 |pmc=2167760 |volume=27 |issue=2 |date=January 1928 |pages=113–59}}</ref> He showed that ''[[Streptococcus pneumoniae]]'', implicated in many cases of [[lobar pneumonia]],<ref name="pmid21576901">{{cite journal |author=Musher DM |title=New modalities in treating pneumococcal pneumonia |journal=Hospital Practice |volume=39 |issue=2 |pages=89–96 |date=April 2011 |pmid=21576901 |doi=10.3810/hp.2011.04.398|s2cid=23884367 }}</ref> could transform from one strain into a different strain. The observation was attributed to an unidentified underlying principle,<ref name = Griffith/> later known in the Avery laboratory as the "transforming principle" (abbreviated as T. P.)<ref>McCarty M. [http://profiles.nlm.nih.gov/CC/A/A/O/F/_/ccaaof.pdf ''The Transforming Principle: Discovering that Genes are Made of DNA''] (New York: W.W. Norton & Co, 1985), p 85.</ref> and [[Avery–MacLeod–McCarty experiment|identified]] as [[DNA]].<ref name="isbn0-89766-905-3">{{cite book |author=Chambers, Donald L. |title=DNA: the double helix: perspective and prospective at forty years |publisher=New York Academy of Sciences |location=New York, N.Y |year=1995 |page=[https://archive.org/details/dnadoublehelix00cham/page/49 49 and p. 185] |isbn=978-0-89766-905-4 |url=https://archive.org/details/dnadoublehelix00cham/page/49 }}</ref> America's leading pneumococcal researcher, [[Oswald T. Avery]], speculated that Griffith had failed to apply adequate [[Scientific control|controls]].<ref name=pmid4143929>{{Cite journal|author=Downie AW |title=Fourth Griffith Memorial Lecture. Pneumococcal transformation—a backward view. |journal=Journal of General Microbiology |pmid=4143929 |volume=73 |issue=1 |date=November 1972 |pages=1–11 |doi=10.1099/00221287-73-1-1|doi-access=free }}</ref> A cautious and thorough researcher, and a reticent individual, Griffith's tendency was to publish only findings that he believed truly significant, and Griffith's findings were rapidly confirmed by researchers in Avery's laboratory.<ref name=pmid4143929/> His discovery was one of the first to show the central role of DNA in heredity.<ref name="isbn0-89766-905-3"/> ==Early life== {{Single strand DNA discovery}} Frederick Griffith was born in [[Prescot]], [[Merseyside]] (formerly in [[Lancashire]]) England, in late 1877<ref name="lancashirebmd">{{Cite web|url=http://www.lancashirebmd.org.uk/pba.php?date=1877&county=lancashire&reference=PT:PRE/40/54&file=G&pos=198537&area=PT&surname_1=GRIFFITH&forename_1=Frederick&year=1877&mmn=|title=Birth certificate Prescot PRE/40/54 for Frederick Griffith on the Lancashire BMD (Births, Marriages and Deaths on the Internet)|website=lancashirebmd.org.uk|access-date=2020-02-04}}</ref> (Registered December quarter in Prescot, Lancashire registration district, vol 8b, page 670), and attended [[Liverpool University]]. Thereafter, he worked at the [[Liverpool Royal Infirmary]], the Joseph Tie Laboratory, and the Royal Commission on [[Tuberculosis]]. In 1910 Fred Griffith was hired by the local government board. ==Ministry of Health office== During [[World War I]] (1914–18), the local government board's laboratory was assumed by the national government, namely UK government, and became the [[Ministry of Health (United Kingdom)|Ministry of Health]]'s Pathological Laboratory—where Griffith was medical officer. UK government spent money sparingly on the laboratory, which remained very basic, though Griffith and his colleague, William M. Scott, "could do more with a kerosene tin and a primus stove than most men could do with a palace".<ref name=pmid4143929/> Griffith was sent pneumococci samples taken from patients throughout the country, amassed a large number, and would type—in other words classify—each pneumococci sample to search patterns of pneumonia epidemiology, and Griffith experimented on mice for improved understanding of its pathology.<ref name=Lehrer>Lehrer S. [https://books.google.com/books?id=cIZpyNvjvdcC&pg=PA47 ''Explorers of the Body: Dramatic Breakthroughs in Medicine from Ancient Times to Modern Science''], 2nd edn (Lincoln NE: iUniverse, 2006), p 47.</ref> Griffith performed the pivotal experiments—actually very many experiments—during the 1920s. With outbreak of [[World War II]] (1939–45), the laboratory was expanded into the Emergency [[Public Health Laboratory Service]]. ==Griffith's Experiment== {{Main|Griffith's experiment}} Pneumococci has two general forms—''rough'' (R) and ''smooth'' (S). The S form is more [[virulent]], and bears a [[Capsule (microbiology)|capsule]], which is a slippery [[polysaccharide]] coat—outside the [[peptidoglycan]] [[cell wall]] common among all classical bacteria—and prevents efficient [[phagocytosis]] by the host's [[innate immune system|innate immune cells]]. Injected [[Subcutaneous injection|subcutaneous]]ly with S form, mice succumbed to pneumonia and death within several days. However, the R form, lacking a capsule—its outer surface being cell wall—is relatively [[avirulent]], and does not cause pneumonia as often. When Griffith injected heat-killed S into mice, as expected, no disease ensued. When mice were injected with a mixture of heat-killed S and live R, however, pneumonia and death ensued. The live R had transformed into S—and replicated as such—often characterized as Griffith's Experiment. More accurately, point six of Griffith's abstract reports that R tended to transform into S if a large amount of live R, alone, were injected, and that adding much heat-killed S made transformation ''reliable''<ref name=Griffith/> Griffith also induced some pneumococci to transform back and forth.<ref name = Griffith /> Griffith also reported transformation of [[serology|serological]] ''type''—bacterial [[antigenicity]]—distinct from presence or absence of a capsule. Bacteriologist [[Fred Neufeld]], of the [[Robert Koch Institute]] in [[Berlin]], Germany, had earlier identified the pneumococcal types, confirmed and expanded by [[Alphonse Dochez]] at Oswald Avery's laboratory in [[United States|America]] at The Rockefeller Hospital.<ref name=Lehrer/> Types I, II, and III were each a distinct antigenic grouping, whereas type IV was a catchall of varying antigenicities not matching other types.<ref name=Lehrer/> Illustrating the plasticity of ''Streptococcus pneumoniae'', the abstract of Griffith's paper reports, "The S form of Type I has been produced from the R form of Type II, and the R form of Type I has been transformed into the S form of Type II".<ref name=Griffith/> ==Impact of Griffith's Discovery== ===Biomedical reception=== One of America's most prominent pneumococcus experts, [[Oswald Avery]], in [[New York City|New York]] at The Rockefeller Hospital—which opened in 1910 on The Rockefeller Institute's campus—initially explained that Griffith's experiments must have been poorly conducted and succumbed to contamination. Avery biographer and colleague at The Rockefeller Institute, microbiologist [[Rene Dubos]], recruited by The Rockefeller Institute from France, later described Griffith's findings as "exploding a bombshell in the field of pneumococcal immunology".<ref>U.S. National Library of Medicine. [http://profiles.nlm.nih.gov/ps/retrieve/ResourceMetadata/CCAAOD "The Oswald T. Avery Collection"]. ''Profiles in Science''. 31 January 2007.</ref> Avery's associate [[Martin Henry Dawson|Martin Dawson]] at The Rockefeller Hospital confirmed each of Griffith's reported findings.<ref name="Dawson">{{cite journal |last1=Dawson |first1=MH |title=The transformation of pneumococcal types: II. The Interconvertibility of Type-Specific S Pneumococci |journal=The Journal of Experimental Medicine |date=1 January 1930 |volume=51 |issue=1 |pages=123–47 |doi=10.1084/jem.51.1.123 |pmid=19869670 |pmc=2131805 }}</ref><ref>McCarty M. [http://profiles.nlm.nih.gov/CC/A/A/O/F/_/ccaaof.pdf ''The Transforming Principle: Discovering that Genes are Made of DNA''] (New York: W.W. Norton & Co, 1985), p 79.</ref> Even before Griffith's publication, Fred Neufeld had confirmed them as well, and was merely awaiting publication of Griffith's findings before publishing his confirmation.<ref name=pmid4143929/><ref name="Levinthal">{{cite journal |last1=Neufeld |first1=Fred |last2=Levinthal |first2=Walter |title=Beiträge zur variabilität der pneumokokken |date=1928 |journal=Zeitschrift für Immunitätsforschung |issue=55 |pages=324–340 |url=http://resource.nlm.nih.gov/101584575X28 |access-date=7 March 2023}}</ref> Over the following years, Avery's illness, [[Graves' disease]], kept him much out of his laboratory as other researchers in it experimented to determine, largely by process of elimination, which constituent was the transforming factor.<ref>McCarty M, ''Transforming Principle''.</ref> Microbiologists endeavored during the 1930s to dispel the monomorphist tenet, prevailing as institutional dogma,<ref>{{Cite journal |author=Kritschewski IL & Ponomarewa IW |pmid=16559732 |title=On the pleomorphism of bacteria. I. On the pleomorphism of ''B Paratyphi'' B"—sec "Summary |journal=Journal of Bacteriology |pmc=533658 |volume=28 |issue=2 |date=August 1934 |pages=111–26|doi=10.1128/jb.28.2.111-126.1934 }}</ref> largely prevailing into the 21st century.<ref>Paracer S and Ahmadjian V. ''Symbiosis: An Introduction to Biological Associations'', 2nd ed (New York: Oxford University Press, 2000), chapter 1, subchapter 1.3, section [https://books.google.com/books?id=OmZ6CfHQIZ8C&pg=PA10 "Bacteria as multicellular organisms"], p 10.</ref> ==Posthumous identification of transforming factor== ===Last days of Griffith and colleague=== The first Griffith Memorial Lecture indicates that Fred Griffith died on the night of 17 April 1941<ref name=Hayes>{{Cite journal|author=Hayes W |url=http://profiles.nlm.nih.gov/CC/A/A/I/K/_/ccaaik.pdf |title=First Griffith Memorial Lecture. Genetic transformation: A retrospective appreciation |journal=Journal of General Microbiology|doi=10.1099/00221287-45-3-385 |volume=45 |issue=3 |year=1966 |pages=385–397|doi-access=free }}</ref>—though the fourth lecture indicates that he died in his apartment in February 1941<ref name=pmid4143929/>—alongside friend and colleague William M. Scott amid an [[strategic bombing|air raid]] during World War II's [[London Blitz]]. A few weeks earlier, Scott had become director of the laboratory, which, with the outbreak of war, had become Emergency Public Health Laboratory Service. Both dated 3 May 1941, his [[obituary]] in ''[[The Lancet]]'' mentioned the historical discovery briefly,<ref>{{Cite journal|doi=10.1016/S0140-6736(00)95174-2 |title=Obituary |journal=Lancet|url=http://profiles.nlm.nih.gov/ps/retrieve/ResourceMetadata/CCBBCC|year=1941|volume=237|issue=6140|pages=588–589}}</ref> and his obituary in ''[[British Medical Journal]]'' failed to mention it.<ref>{{Cite journal|doi=10.1136/bmj.1.4191.691 |title=The 'English Disease'|year=1941|last1=Bacharach|first1=A.L.|journal=British Medical Journal|volume=1|pages=691|issue=4191|pmc=2161843}}</ref> ===Avery ''et al'' then Watson & Crick=== In 1944 identification of the transforming factor was published in the ''[[Journal of Experimental Medicine]]'' by Avery, [[Colin Munro MacLeod|Colin MacLeod]], and [[Maclyn McCarty]] of The Rockefeller Hospital.<ref>{{Cite journal|doi = 10.1084/jem.79.2.137|title=Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types – Induction of Transformation by a Desoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III|last1=Avery|first1=Oswald T|last2=MacLeod|first2=Colin M|last3=McCarty|first3=Maclyn|journal=[[Journal of Experimental Medicine]]|pmid=19871359|pmc=2135445|volume=79|issue=2|date=February 1944|pages=137–58}}</ref> This identification departed from the prevailing belief that the ''protein'' content of [[chromosome]]s probably was the anatomical structure of genes, although it would take another decade—till [[James D. Watson|Watson]] and [[Francis Crick|Crick]]'s 1953 [[Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid|paper]] in ''[[Nature (journal)|Nature]]'' indicating DNA's molecular structure suggesting how a molecule as seemingly simple as DNA could encode the structure of proteins—for the interpretation of DNA as genes to become widely accepted.<ref>{{Cite journal|doi=10.1038/nature01398 |title=Discovering genes are made of DNA |author=McCarty M |journal=Nature|pmid=12540908 |volume=421 |issue=6921 |date=January 2003 |pages=406|bibcode=2003Natur.421..406M |doi-access=free }}</ref><ref>{{cite journal | last1 = Anderson | first1 = ES |date=Sep 1985 | title = The road to DNA | url = https://books.google.com/books?id=JGhFy902N6UC&pg=PA53 | journal = New Scientist | volume = 107 | issue = 1474| pages = 53–4 }}</ref> ===Applications=== Biologists made little more than speculation of Griffith's report of transformation until genetics research in 1951.<ref>{{Cite journal |author=Lederberg J |title=Notes on the biological interpretation of Fred Griffith's finding |journal=American Scientist |url=http://profiles.nlm.nih.gov/ps/retrieve/ResourceMetadata/CCAAQX}}</ref> Griffith's report was virtually ignored by [[clinicians]], and by the medical sector as a whole.<ref name=pmid4143929/> ==Griffith's further work and legacy== [[Image:Fred Griffith and "Bobby" 1936.jpg|thumb|right|190px|Fred Griffith in 1936]] ===Bacteriology=== In 1931 Frederick Griffith coauthored a paper on acute [[tonsillitis]]—its [[sequelae]], epidemiology, and bacteriology.<ref>{{Cite journal |author=Glover JA & Griffith F |title=Acute tonsillitis and some of its sequels: Epidemiological and bacteriological observations |journal=British Medical Journal|doi=10.1136/bmj.2.3689.521|year=1931|volume=2|issue=3689|pages=521–7|pmid=20776393|pmc=2315140}}</ref> In 1934, Griffith reported voluminous findings on the serological typing of ''[[Streptococcus pyogenes]]''.<ref>{{Cite journal|author=Griffith F |title=The serological classification of ''Streptococcus pyogenes''|journal=Journal of Hygiene|pmid=20475253 |pmc=2170909 |doi=10.1017/S0022172400043308 |volume=34 |issue=4 |date=December 1934 |pages=542–84}}</ref> More casually as well as medically called simply streptococcus,<ref>Kenneth Todar [http://www.textbookofbacteriology.net/streptococcus.html "''Streptococcus pyogenes'' and streptococcal disease (page 1) "]. ''Todar's Online Textbook of Bacteriology''. 2008.</ref> ''S pyogenes'' is implicated in conditions ranging from the usually minor [[strep throat]], to the sometimes fatal [[scarlet fever]], to the often fatal [[puerperal fever]], to the usually fatal [[streptococcal sepsis]].<ref>{{Cite journal|title=Streptococcal sepsis |journal=British Medical Journal|pmid=5198333 |pmc=1699551 |doi= 10.1136/bmj.1.5695.513 |volume=1 |issue=5695 |date=February 1970 |pages=513–4}}</ref> Streptococcal infection was a frequent coinfection complicating recovery from lobar pneumonia by pneumococci infection.<ref>{{Cite journal|doi=10.1001/jama.1933.02740230035007 |title=Streptococcic sepsis complicating recovery from pneumococcal pneumonia |journal=Journal of the American Medical Association|author=Parsons JW & Meyers WK |year=1933|volume=100|issue=23|pages=1857}}</ref> ===Medicine=== By 1967 pneumococcal transformation had been shown to occur ''[[in vivo]]'' naturally, and it was further shown that treatment with [[streptomycin]] during dual infection by two pneumococcal strains could increase transformation—and virulence—while for the first time pneumococcal transformation was shown to occur in the respiratory tract.<ref>{{Cite journal|author=Conant JE & Sawyer WD |title=Transformation during mixed pneumococcal infection of mice |journal=Journal of Bacteriology|pmid=4381631|pmc=276704|volume=93|issue=6|date=June 1967|pages=1869–75|doi=10.1128/jb.93.6.1869-1875.1967 }}</ref> In 1969 it was shown ''in vivo'' that during drug treatment of a host, pneumococci could acquire genes from [[Antibiotic resistance|antibiotic-resistant]] streptococci, already in the host, and thereby the pneumococci could become resistant to [[erythromycin]].<ref>{{Cite journal |author=Ottolenghi-Nightingale E |title=Spontaneously occurring bacterial transformations in mice |journal=Journal of Bacteriology|pmid=4390504|pmc=315412|volume=100|issue=1|date=October 1969|pages=445–52|doi=10.1128/jb.100.1.445-452.1969 }}</ref> ==References== {{Reflist}} {{Authority control}} {{DEFAULTSORT:Griffith, Frederick}} [[Category:1877 births]] [[Category:1941 deaths]] [[Category:Alumni of the University of Liverpool]] [[Category:20th-century English scientists]] [[Category:British civilians killed in World War II]] [[Category:Deaths by airstrike during World War II]] [[Category:English bacteriologists]] [[Category:English pathologists]] [[Category:Genetics in the United Kingdom]] [[Category:History of genetics]] [[Category:People from Hale, Greater Manchester]]'