Frederick Griffith (1879–1941) 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,
the first widely accepted demonstrations of bacterial transformation,
whereby a bacterium distinctly changes its form and function.
He showed that Streptococcus pneumoniae, implicated in many cases of
lobar pneumonia, could transform from one strain into a different
strain. The observation was attributed to an unidentified transforming
principle or transforming factor. This was later identified as
DNA. America's leading pneumococcal researcher, Oswald T. Avery,
speculated that Griffith had failed to apply adequate controls. 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. His discovery was one of the
first to show the central role of
DNA in heredity.
1 Early life
2 Ministry of Health office
3 Griffith's Experiment
4 Impact of Griffith's discovery
4.1 Biomedical reception
5 Posthumous identification of transforming factor
5.1 Last days of Griffith and colleague
5.2 Avery et al then Watson & Crick
6 Griffith's further work and legacy
John Masson Gulland
Sir John Randall
Frederick Griffith was born in Hale,
Lancashire county, England, in
late 1879 (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
World War I
World War I (1913–18), the local government board's
laboratory was assumed by the national government, namely UK
government, and became the 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
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. Griffith performed the pivotal
experiments—actually very many experiments—during the 1920s.
With outbreak of
World War II
World War II (1939–45), the laboratory was expanded
into the Emergency Public Health Laboratory Service.
Main article: Griffith's experiment
Pneumococci has two general forms—rough (R) and smooth (S). The S
form is more virulent, and bears a 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 cells. Injected subcutaneously 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 Griffith also induced some pneumococci
to transform back and forth.
Griffith also reported transformation of 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
Alphonse Dochez at Oswald Avery's laboratory in America at
The Rockefeller Hospital. Types I, II, and III were each a distinct
antigenic grouping, whereas type IV was a catchall of varying
antigenicities not matching other types.
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".
Impact of Griffith's discovery
One of America's most prominent pneumococcus experts, Oswald Avery, in
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".
Martin Dawson at The Rockefeller Hospital confirmed
each of Griffith's reported findings. Even before Griffith's
Fred Neufeld had confirmed them as well, and was merely
awaiting publication of Griffith's findings before publishing his
confirmation. 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.
Microbiologists endeavored during the 1930s to dispel the monomorphist
tenet, prevailing as institutional dogma, largely prevailing into
the 21st century.
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—though the fourth lecture
indicates that he died in his apartment in February
1941—alongside friend and colleague William M. Scott amid an 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, and his obituary in British Medical Journal
failed to mention it.
Avery et al then Watson & Crick
In 1944 identification of the transforming factor was published in the
Journal of Experimental Medicine by Avery, Colin MacLeod, and Maclyn
McCarty of The Rockefeller Hospital. This identification departed
from the prevailing belief that the protein content of chromosomes
probably was the anatomical structure of genes, although it would take
another decade—till Watson and Crick's 1953 paper in 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.
Biologists made little more than speculation of Griffith's report of
transformation until genetics research in 1951. Griffith's report
was virtually ignored by clinicians, and by the medical sector as a
Griffith's further work and legacy
Fred Griffith in 1936
Frederick Griffith coauthored a paper on acute
tonsillitis—its sequelae, epidemiology, and bacteriology. In
1934, Griffith reported voluminous findings on the serological typing
of Streptococcus pyogenes. More casually as well as medically
called simply streptococcus, 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. Streptococcal infection
was a frequent coinfection complicating recovery from lobar pneumonia
by pneumococci infection.
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. In
1969 it was shown in vivo that during drug treatment of a host,
pneumococci could acquire genes from antibiotic-resistant
streptococci, already in the host, and thereby the pneumococci could
become resistant to erythromycin.
^ a b c d e Griffith F (January 1928). "The significance of
pneumococcal types". Journal of Hygiene. 27 (2): 113–59.
doi:10.1017/S0022172400031879. PMC 2167760 .
^ Musher DM (April 2011). "New modalities in treating pneumococcal
pneumonia". Hospital Practice (1995). 39 (2): 89–96.
doi:10.3810/hp.2011.04.398. PMID 21576901.
^ a b Chambers, Donald L. (1995). DNA: the double helix: perspective
and prospective at forty years. New York, N.Y: New York Academy of
Sciences. p. 49 and p. 185. ISBN 0-89766-905-3.
^ a b c d e f Downie AW (November 1972). "Fourth Griffith Memorial
Lecture. Pneumococcal transformation—a backward view" (PDF). Journal
of General Microbiology. 73 (1): 1–11. doi:10.1099/00221287-73-1-1.
^ a b c Lehrer S. Explorers of the Body: Dramatic Breakthroughs in
Medicine from Ancient Times to Modern Science, 2nd edn (Lincoln NE:
iUniverse, 2006), p 47.
^ U.S. National Library of Medicine. "The
Oswald T. Avery
Oswald T. Avery Collection".
Profiles in Science. 31 January 2007.
^ McCarty M. The Transforming Principle: Discovering that Genes are
DNA (New York: W.W. Norton & Co, 1985), p 79.
^ McCarty M, Transforming Principle.
^ Kritschewski IL & Ponomarewa IW (August 1934). "On the
pleomorphism of bacteria. I. On the pleomorphism of B Paratyphi
B"—sec "Summary". Journal of Bacteriology. 28 (2): 111–26.
PMC 533658 . PMID 16559732.
^ 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 "Bacteria as multicellular
organisms", p 10.
^ Hayes W (1966). "First Griffith Memorial Lecture. Genetic
transformation: A retrospective appreciation" (PDF). Journal of
General Microbiology. 45: 385–397.
^ "Obituary". Lancet. 237 (6140): 588. 1941.
^ Bacharach, A.L. (1941). "The 'English Disease'". British Medical
Journal. 1 (4191): 691. doi:10.1136/bmj.1.4191.691.
^ Avery, Oswald T; MacLeod, Colin M; McCarty, Maclyn (February 1944).
"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"
(PDF). Journal of Experimental Medicine. 79 (2): 137–58.
doi:10.1084/jem.79.2.137. PMC 2135445 .
^ McCarty M (January 2003). "Discovering genes are made of DNA".
Nature. 421 (6921): 406. doi:10.1038/nature01398.
^ Anderson, ES (Sep 1985). "The road to DNA". New Scientist. 107
^ Lederberg J. "Notes on the biological interpretation of Fred
Griffith's finding". American Scientist.
^ Glover JA & Griffith F (1931). "Acute tonsillitis and some of
its sequels: Epidemiological and bacteriological observations".
British Medical Journal. 2 (3689): 521–7.
doi:10.1136/bmj.2.3689.521. PMC 2315140 .
^ Griffith F (December 1934). "The serological classification of
Streptococcus pyogenes". Journal of Hygiene. 34 (4): 542–84.
doi:10.1017/S0022172400043308. PMC 2170909 .
^ Kenneth Todar "
Streptococcus pyogenes and streptococcal disease
(page 1) ". Todar's Online Textbook of Bateriology. 2008.
^ "Streptococcal sepsis". British Medical Journal. 1 (5695): 513–4.
February 1970. doi:10.1136/bmj.1.5695.513. PMC 1699551 .
^ Parsons JW & Meyers WK (1933). "Streptococcic sepsis
complicating recovery from pneumococcal pneumonia". Journal of the
American Medical Association. 100 (23): 1857.
^ Conant JE & Sawyer WD (June 1967). "Transformation during mixed
pneumococcal infection of mice". Journal of Bacteriology. 93 (6):
1869–75. PMC 276704 . PMID 4381631.
^ Ottolenghi-Nightingale E (October 1969). "Spontaneously occurring
bacterial transformations in mice". Journal of Bacteriology. 100 (1):
445–52. PMC 315412 . PMID 4390504.