Volume 13 No 1
March 1992
ISSN 0965-0989
1,
I
I
Dental plaque: commensalism,
conflict and control
Joseph Listersurgeon/microbiologist
Philip D Marsh ,
Eric Bridson ,
Group Head,
PHLS Centre for Applied
Mic rob iology & Research,
Salisbury, an d Honorary Senior
Lecturer in Oral Microbiology,
University of London.
Technical Consultant ,
Unlpath Limited.
Basingstoke,
Hants , UK.
A review of the microbia l
colonisation of teeth and
strategies for its contro l.
An account of the li fe of the
founder o f antiseptic surgery
and a pioneer of preventive
medicine.
Dental plaque: commensalism,
conflict and control
Philip D Marsh , BSe, PhD, Group Head, PH LS Centre for Applied Microbiology & Research,
Sal isbury, and Honorary Senior Lecturer in Oral Microbiology, University of London .
Introduction
In the body. tee th provide unique structures
for microbial colonisation. They are hard. nonshedding surfaces which allow for the accumulation of large masses of micro-organisms.
Elsewhere In the body. microbes colonise
epithelial surfaces, and desquamation ensures
Ihat the microbial load at these sites is light
After eruption, teeth are rapidly colonised
by bactena. Bacteria embedded in a matrix
of polymers of salivary and bacterial origin,
constitute denial plaque. DenIal plaque
forms naturally on teeth. and has beneficial
properties. for example. In preventing colonisation by exogenous (and often pathogenic)
micro-organisms. I In the absence of adequate
oral hygiene, den tal plaque can accumulate
beyond levels compa tible wi th heal th, This
accumulation can lead to shifts in the balance of the microflora, and under app ropriate conditions and at a susceptible site,
dental caries or periodontal (gum) diseases
can occur (Figure 1). Althougll rarely li fethreatening, these diseases are highly prevalent in Industrialised societies and are
extremely costly to treat In Britain for
example, the cost of dental treatment to the
National Health Service alone IS In excess of
[800.000.000 per annum. The aim 01 Ihis
article will be to describe bnefly the changes
that take place In plaque during its transition
from having a role in health to being associated wi lh disease. and 10 highlighl some ol lhe
strategies currently being employed to
cont rol plaque and preve nt disease
Microbial compositio n 01 dental p laque
Rece nt advances in isolation proced ures
and mic robia l classi fication schemes have
Enamel
Enamel
caries
Dentine
PUlp ----~~@~';:;!T.;r
Gingival crevlC"·. ______'-..
Gum - _ _ _"""'0::::
Periodontal
pockel
Cementum
--2:...:..24,,1 I
Allachmenl
fibres
Alveolar bone
-
--'---'-
Figure 1: Tooth structure in health and disease.
shown that the reSident plaque microflora
is diverse (Tab le 1), and contains species
unique to the mouth. The predominant
speCies overlying sound enamel belong to
the genera SlrepiOCOCClJs. Actinomyces,
Vellfonella and Haemophilus.2.3 In disease.
the balance of the microflora is pertu rbed ;
the microbia l diversity of plaque is increased sti ll further, whi le some previously minor
componen ts become predomi nant. These
Table 1: Bacterial genera found in dental
ptaque.
GRAM-POSITIVE
cocci
Streptococcus
Peptostreprococcus
GRAM-NEGATIVE
cocc i
Neisseria
Veillonella
Saliva
components
promoting
aUachment
01 cell 8, 10
{~
Actinomyces
Bifidobacterium
Corynebacterium
Eubacterium
Lactobacillus
Propionibacterium
AorfJia
species 8 to cell
c
.-':
~
t
~
Co-aggregation 01
2
I
1
rods
Campy/obacter
Capnocytophaga
Eikenelfa
Fusobacterium
HaemoplJifus
Leptotrichia
Prevotelfa
Selenomonas
changes are deSCribed in more detail in a
later section.
Teeth do not provide a uniform habitat for
micro-organisms but have several distinct
sur faces which . because of their biological
proper ties, are suitable for colonisation by
only certain species. For example , the
ging iva l crevice (Figure 1). where the tooth
• rises out of the gum, has the lowest redox
poten tial and is also bathed by g ing ival
J::r
l
}~~:~~~IS
Sal1va
8
8,.
rods
_ - - Riool caries
A.
~v ~
,/
A
Pellicle
.......
attachment of
species C by
saturating
}
0
9
d
receplors on its
cell surt.ce.
gtU g~ ~ t g! t ~ g~ !t
Adhesins
~~£~~~::
with different
receptors in
Ihe pellicle.
~/////;@/////&
Enamel
Notes : Most genera contain more than one
species. Some of these genera are present
only in low numbers at heallhy sites; additional
genera can be isolated at diseased sites.
2
Figure 2: A diag rammatic representation of some of the stages in vo lved in pl aqu e formation .
(Reproduced wit h permission .)3
I
f
i
I
,-I
Figure 3: Scan ning electron micrograph of dental plaque showing cocci , rods, and filamentousshaped cell s, as well as ' corn-cob' associations. (Original magnification x 2,000; courtesy of KM
Pang .)
crevicular fluid (GCF, a se rum-like exudate) . GCF. in addition to containing componen ts of the host defences. also provides
nutrients (in the form o f proteins and
gl ycoproteins) for the resident mlcroflora of
this site. Consequen tly. the gingival crevice
harbours the highest propor tions of obligate ly anae robic and nutritionally fastidious
bac teria.
Deve lopme nt of dental plaque
As soon as a tooth su rface is cleaned, com-
ponents in saliva are adsorbed ontoenamei
10 form lheacqui red pellicle( Figure 2). This
pe ll icle conta ins proteins and glycoprotelns,
and acls as a 'conditioning film ' by p romo ting the adherence of ce rtain species . For
examp le. acidic proline-rich proteins (PRPs)
and sta th erin act as receptors for adllesins
on Actinomyces viscosus, and some st rains
of Streptococcus mutans. and on blac kpigmented anaerobes -I Recently, it has
been shown that A. viscosuscan b ind avidly
10 certain PRPs only when they are adsorbed to a surface but not when they are in
so lution . This is due to hidden receptors
('cryp tilopes') on PRPs becoming exposed
due to conformational changes when Ihe
protein is adsorbed to enamel.-I Amylase .
immunoglobul ins, lysozyme. and albumin
have also been detected in th is pellicle, as
have some bacterial components such as
glucosyltransferases (GTFs). In pe llicle.
these enzymes can syn thesise glucans
from suc rose that bind to receptors (glucanbinding proteins) on some streptococc i.
A number 01 non-specific and specific
interactions occur wh en a cell approaches
pellicle-coated enamel (Figure 2 ).? -I These
interac tions will determine whether coloni sation will occur. and inc/ude:
a) Van der Waals attractive forces at relatively long separation distances (>50
nm). and a weak area of allrac ti on (the
'secondary minimum') at shorter separation distances ( 10- 20nm).
b) Specific short range interactions between
bac teri al adhesins on tile cell surface
and host recep tors, thereby in c reas ing
Figure 4: Cross-section through dental plaque showing micro-colony sub-structure. (Courtesy of
JM Hardie.)
the strength of attachment over these
and shorter distances (Fig ure 2). For
example, many plaque bac teria have
galactosyl-binding lectins thai bin d to
the appropriate sugar residue in the
ol igosaccharide side-chains of adsorbed
salivary glycoproteins (mucins).4 These
residues are exposed once fhe terminal
sialic acid has been removed by
neuraminidase, which is produced by
streptococci and Aclinomycesspp.
c) The co-aggregation of bacteria to already
attached cells. S Co-aggregation can
occur between Gram-positive species,
between Gram-negative species, and
between Gram-positive and Gramnegative species. This can lead to unusual physical combinations of bacteria
such as the 'corn~cob ' strucures shown
In Fi gure 3 . These associations can be
between, for example, certain streptococci and Corynebacterium matruchotii,
and between Veilfonella and Eubacterium.
d) The mul tiplication of these attached ce lls
to produce micro-colonies. At stagnan t
sites, continua l cell division with in these
micro-colonies can eventually lead to
confluent growth and the development of
a complex biofi lm in which th ere can be
a heterogenous sub-structure (Figure4).
Numerous types of microbial interactions
occur during dental plaque formation .
Foodwebs develop whereby the prod uct of
one spec ies becomes a primary nutrien t
source for others (e.g . lactate produ ced by
streptococci is utilised by Veilfonella spp.),
and several species may co-operate in order
10 degrade complex hOSI molecules such
as saliva ry glycoproteins. In con trast, some
species produce antagonistic substan ces
(e.g . bacleriocins, hydrogen peroxide,
acids) tha t may improve their abi lity to
colonise or predominate at a sile.2.3
Dental plaque and d isease
Plaque pre ferentially accumulates at retentive or stagnan t sites (Figure 5) from wh ere
It is difficul t to remove except by diligent oral
hygiene. As tile plaque mass increases. the
benef icial buffering and an ti microbial properties of saliva are less able to pe net rale
and protec t the enamel, and there is a
concomi tant shift in the balance of tile
predominant bacteria away from those
associated with health. The microbiological
characteristics of the two main dental
d iseases will now be described in brief
Dental caries
Tile rest ing pH of plaq ue is around neutralily due to the buffering action of saliva . The
consumption o f dielary sugars leads to the
rapid production of acid (mainly lactic acid)
in plaque by glycolysis, so that the pH can
fal l below 5.0 within a few minutes, and
remain at such values for some time,
causing ename l to demineralise. As the pH
gradually returns to resting values, enamel
remineralises. However, in subjec ts who
repeatedly ingest fermentable dietary
suga rs. the pH in p laque falls lower more
often and for longer periods. Th is shift s the
equil ibrium in favou r of demineralisation,
and leads eve ntually to the formation of a
caries lesion (Figure 1). These condilionsof
low pH are inhibitory for many species
associa ted wi th sound enamel but favou r
3
the growth 01 highly acidogenic and cariogenic organ isms such as mutans streptococc i(e.g. 5.mu /ans. S. sobrinus) and lactobaci lli. 3.G In the young. caries is primarily 01
enamel surfaces (especially 01 occlusal
fissures and approximal surfaces be tween
teeth). while caries of tile root surface is
becom ing a major problem in the elderly
due to recession of the gums in old age
(Figure 1).
Periodontal diseases
The term 'periodon tal diseases· embraces
a number 01 diseases in whicll the supporting tissues of the teeth are attacked . The
junctional epithelium at the base of the
gingival crevice migrates down the root of
ille tooth to form a periodonta l pockel
(Figure 1). In advanced stages of disease.
attachmen t fibres and alveolar bone are
also lost. Frequently tile predominan t bacteria in periodon tal pockets are obligately
anaerobic or CO ,,-requiring (capnoph ilic)
Gram-negative rods. filaments Of spiralshaped bacteria. many of which are
nutri tionally fastidious and difficul t to grow
in the labora tory}. 7 Recen t research has
iden tified several new species unique to tlris
habitat. Tissue destruction is caused by the
produc tion of bacterial proteases and cytotoxins. as well as by the damaging sideeffecls of th e host inflammatory response to
the increase In plaque.3 Among the species
mos t deeply implicated in the various forms
of periodontal disease are Prevo/ella intermedia. Porphyromonas gingivalls. Actinobacilfus actinomycelemcomitans, Fusobacterium !1l1e/eatlltn. Campy/obaeter rectus.
and several poorly charac terised Treponemaspecies. 3.7
Approaches to control dental plaqu e
and prevent disea se
The mechanical remova l of plaque by
efficient oral hygiene (b rushing and flossIng)can alrnost comp letely p revent plaquemed iated dental diseases , Such measures
are par ticul arly effec tive when cornbi ned
with a reduction ',n the amount and frequency
of sugar intake. As It is difficu lt to alter established eating habits and to maintain a hig h
degree of motivation for effective oral hygiene. alternative preven tive measures are
be in g developed that require minimal activi ty by the individual for their effectiveness
Tabte 2: Examples of antimicrobial agents used in toothpastes and mouthwashes for plaque
control.
ANTIMICROBIAL AGENT
EXAMPL E
Bisbiguanides
Chlorhexidine
Enzymes
GJucanase; amyloglucosidase/glucose oxidase
'Essential oils'
Thymol; eucalyptol
Metal salts
Stannous; zinc
Plan t extracts
Sanguinarine
Phenols
Triclosan
Quaternary ammonium compounds
Cetylpyridinium chloride
Fissure sealants
Caries-prone occlusal fiss ures can be
protected by the application of strongly
adllerent. sell-polymerising and UV-ligll t
polymerising plastic sealants.
Fluoride
Fluoride. whether delivered via drinking
water. toothpastes, topical varnishes or til e
diet. can lead to dramatic (>50%) reductions In the Incidence of dental caries . Tile
primary mode of action of fluoride is to
st rengthen enamel against acid attack.
FlUOride is incorporated into enarnel to form
fluorapati te; fluorapatite is tllermodynamically more stable than apatite. and hence
resists acid dissolution to a greater ex tent.
Fluori de may also exert some subtle an timicrobial effects by interfering wi th bacterial
metabolism, e.g . by inhibiting enolase and
hence sugar metabol ism and acid prod uction.8The susceptibility of bacteria (espeCially
mu tans streptococci) to fluoride is enhanced
at low pH. and so it ac ts optimally under the
conditions wilen It is most needed by the
host.
Sugar substitutes
Most people enjoy eati ng sweet substances:
unfor tunately. rnany sweet foods contai n
mono - and disaccharides that are readily
metabolised to acid by plaque bac teria If
they are eaten frequent ly. tile ris k of dental
caries is increased. To satisfy' the human
The Oxoid Streptococcal Grouping KitDesigned for convenience
TIle Oxoid Streptococcal Grouping Ki t has been introduced by Unipath Ltd. to tile
Oxoid range of Diagnostic Reagen ts. The streptococcal groupi ng reagents are
suppl ied as bl ue latex suspensions. The la tex particles are coated wi th group spec ific
an tibodies Wll ich agglu ti nate in the presence of homologous antigen . The resulting
blue lattice struc ture is clearly vis ible against the white background of the new
disposable reaction slides .
The reagents accurately identify the streptococcal groups, incl uding group D in
strains wllere D and G cause misidentification with othe r tests .
Tile new kit Ilas colou r coded bot tles to facilitate the selec tion of each grouping
reagent. The packaging has been designed as a compact and easy to store work station.
For further inlonnation co ntact: Mrs V Kane. Unipath Ltd , Wade Road. Basingstoke.
Hanls RG24 OPW England Tet : (0256) 84114 4. Fax : (0256) 463388. Telex : 858793
4
preference for sweet substances. dietary
sweetene rs that are not (or only slowly)
metabolised by p laque bacteria can be
used. Intense sweeteners such as cyclamate. aspar tame and saccha rin are now
used in drinks. g , 10 while bulk agen ts such
as sugar alcohols (e.g, sorbitol. xyl itol) are
used in confec tionery. 10 In addi tion to being
only poorly rnetabolised by plaque bac teria.
some sugar substitutes have other beneficial effects. Thei r ability to stimula te saliva
flow In the absence of significant acid
production can lead to the reminera lisation
of enamel. Furthermore. xylitol can interfere
wi th sugar metabolism and selec tively inIlibit tile growth and metabolism of mutans
streptococci. People who habi tually consume products containing xylitol Ilarbour
lower levels of these cariogenic bacteria,
and have a reduced caries experience.
Antimicrobial and antiplaque agents
Antimicrob ial agents can be delivered by
tooth pastes and mouthwashes to control
ptaque and prevenl disease (Table 2).
Initially. such agents may be presen t for a
limi ted time at relatively high concen trations
(>M1C). and thereafter operate for longer
periods at sub- MIC levels. The most effective agent to date has been tile broad
spectrum antimicrobial agent chlorhexidine.
Wllich can reduce plaque. ca ries and gingivitiS in humans. 11 It can be delivered by
mouthwash and gel. and also applied as a
-----------------------
j
!l
c!'
'0
I
i
~
Fig ure 5: Teet h (left ) apparentl y health y on first presentation by 7·yea r-o ld . Disc los ing solution reveals plaque accumulation (right) after 30 seco nds .
Blue s tain areas reveal plaqu e less Ih an 24 hours o ld . Pink stain reveals pla qu e more than 24 hours old.
varnish over teeth and is not recommended
for prolonged use without supervision. Even
when present In the mouth al sub·MIC levels.
chlorhexldlne can interfere with several
aspects of bacterial metabolism implicated
in disease (e,g. acid production. sugar
transport, protease activity), Other agents
found in mouthwashes include surfactants.
quaternary ammonium compounds and
'essential oils' (thymol, eucalyptol etc.).
Some agents are compatible for formu·
ra tion in to toothpastes, and there are several
products curren tly being marketed that
provide antimicrobial benefit in addition to
that provided by fluoride and surfactants 12,13
These agents, including Trtclosan and
various metal salts(e.g. Zinc, stannous). are
bactericidal at high concentrations, and
inhibi t me tabolism (glyco lysis, p rotease
activity) at lower levels. Enzymes such as
glucanases have been used to reduce
adherence and plaque formation, while
products containing glucose OXidase and
amyloglucosldase are intended to generate
hydrogen peroxide from carbohyd rates to
boost the activity of the salivary peroxidase
antimicrobial system. Another promiSing
area IS the use of natural plant extracts that
possess anltmlcrobial or anti plaque effects.
In the future, It IS hoped to deliver molecules
to the tOOtll tha t co uld mOdify the properties
of the surface and so prevent or reduce
microbial attachment. Irrespective 01 the
mode of action of these antllTIlcroblal and
anti plaque agents. care has to be taken to
ensure that their regular use leads neither to
the deleterious d isruption 01 the na tural
ecology 01 Ihe oral microflora (e.g. by the
overgrowth of exogenous species) nor to
the development of reSistance
Vaccination
Saliva and GCF provide the mouth with all 01
the components necessary to mount an
effective Immune response against mtcro·
organisms. Although the microbial aetiology
of caries is not totally monospecific, considerable evidence implicates mutans st reptococci (especially S.mUlans and Ssobrinus)
as the major group of causative bacteria. 6
ThiS has led to the development of sub-unit
anti -caries vaccines using speCific antigens
from mutans streptococci as immunogens. l -1
These antigens include GTFs, and other
defined surface proteins. some of which may
also be involved in the adherence of
S.f7lutans to enamel These vacCines have
been shown to be effective in reducing
caries in rodent and primate models, but no
human trials have yet been commissioned.
During the period of vaccine development,
the Incidence of canes has fallen dramatic·
ally in many countries, probably as a result of
fluonde. so that the need for such vaccines
has diminished . Moreover, a major question
faCing Ilealtll organisations is wllether vaccination against a non-life·thrcatening dis·
ease IS lustlfled Recently. however. It has
been demonstrated that the topical application of monoclonal anllbodles directed
aga inst antigens from mutans streptococcI
could preven t colonisation 01 teeth by these
cariogenic bacteria In humans. and protect
against cartes In primates. ThiS approach
might form the baSIS of an a!ternatlve canesprevention strategy In tile future
Concluding remark s
The use of fluoride, a greater awareness of
dental issues. and Improvements to the diet
have led to a marked reduction In the In·
cldence of dental caries in the young. As
people retain their teeth Into later life.
plaque will continue to pose a threat to the
dentition, and rool surface canes and periodontal diseases will become an increasing
problem. New, more effec tive strateg ies are
actively being sought to reduce the impact
of plaque-mediated diseases while, at the
same lime. preserving the beneficial properties of the reSident microflora 01 the oral
cavity. I!!
References
1 Marsh , PD(1989) J Oellf Res 68 :1 567 1575
? Thcllade. E (1990) In Human Mlcrobl8l Ecology
(I hll and Marsh. Eds), CAC Press. Boca Raton
pp 1 56
3 Marsh. P and Marlin, M (1992) Oral M,crobIO·
logy. 3rd Ed., Chapman and Hall . London.
1\ Gibbons. R J (1989) J Oem Res, 68: 750 760
5 Kolenbrander, PE (1988), Ann. Rev Microbial
42:627 656
6 Loesche, WJ , (1986) Mlcroblol Rev 50: 353
380
7 Socransky. S,S" Hat/ajee.A,D " Smith, G.L F and
D... mk,JL(I987) J elm Peflodo1l101 14 : 588
593
8 Hamilton . I R and Bowden. G H (1988) In
Fluoflde III Dentistry (Ekslrand, Fejerskov and
Silverstone. Eds), Munksgaard , Copenhagen,
pp77 103
9 Grenby,TH (1991) 1m Dell( J 41 : 217 224
10 Grenby, TH (Ed) (1989) Progress III
Sweeteners Elsevier, london
II Glermo. P (1989) J Oem Res 68 : 1602 1608
12 Schele, A Aa (1989) J Dent Res 68: 1609
1616
13 Mnrsh , PO (1991) J Clm Peflodorl/ol 18 :
462 467
11\ Krassc. B . Emlison. C. and Gahnberg. L. (1987)
Cclnes Res 21 : 255 276
IS M<1fSh.P D (1991) , Bfll DentJ 171 : 174 177
Medium for the Detection of Motile Salmonellae
Un ipatll Ltd have extended their Oxoid Culture media range 10 Include Modified SemtSolid Rappaport Vasstliadls (MSRV) Medium Deve!oped for the detection of motile
Salmonella spp. from food and environmental samples thiS IS a semi·solid medium It is
made selective by the Incorporation of malachite green and magnesium chloride into
MSRV Medium Base (Code CM910). Selectivity is increased by the addition 01 MSRV
Selective Supplement. (Code SR 16 1) which contains novobiocin. Tile concentration of
agar produces a gel tllrough which motile Salmonella spp. can migrate .
MSRV Medium Base (Code CM9tO) is available in packs 01 500 grns MSRV
Selective Supplement (Code SRI61) is available In packs of 10 vials, each vial
supplements SOOml of medium.
For further informatron contact Mrs V Kane, Unlpath Ltd, Wade Road, Baslngstoke,
Hants RG24 OPW England Tel : (0256)84tt44. Fax: (0256) 463388. Telex : 858793.
5
Joseph Listersurgeon/microbiologist
Eric Bridson, CBiol, FIBiol, FIMLS, Technical Consultant, Unipath Limited, Basingstoke, Hants,
UK.
Introductio n
Joseph lister (Figure 1) came from a pros-
perous and hard-working Quaker family
His father, Joseph Jackson Uster, was a man
of remarkable attainments Although his
educalion fin ished when he was only 14
years of age. he was an excellen t scho lar
and pursued his talents in the study of
optics. He Investigated the optical properties of different types of glass and
anticipated the later discoveries of Abbe
and others. This researcll ea rned him a
Fellowship of the Royal Society in 1832. His
talent fororiglnal researCh, lucidity although!
and mathematical accuracy must have
influenced his children , especially his son
Joseph. who was born on April 5th 1827
Young Joseph Lister
He was the fourth child and second son,
raised with his family in a tranquil and thrifty
Quaker household. HIS mother, Isabella
(nee Hams). had been a school-mistress
Figu re 1: Joseph Lister (centre) wit h colleag ues at Liverpool.
and she. together with the rest ol lhe family
covery of anaesthetiCS. thus he was spared
and frie nds. shaped and influenced Josepl~'s
life. AI schoOl In London. Joseph was bright
but not exceptional and he left with a good
grasp of classics. mathematics. natural
science and modern languages. However,
during this penod of his education he star t-
tile gagged and bound patient wr ithing
under the surgical knife . However. he had to
face the appalling sepsis and gangrene
which seemed Inevitably to follow surgery. It
made a lasting impression In young Lister's
ed dissecting fish and small animals. He
then announced his intention 10 become a
surgeon
At the age of 17 he began hiS studies al
University College. London obtaining hiS
BA in 1847 Medical studies fo llowed in
1848 at University College Hospi tal and he
added his BMed and became a Fellow 01
the Royal Collegeol Surgeons. Joseph Lister
began hiS surgical career alter the dls-
mind (Figure 2).
The surgeon
Lister was adVised by Sharpey (the greal
phYSiologist) loget experience of surgery in
Edinburgh and to visit the famous hospitals
of Europe. Accordingly, he wenl to Edinburgh
in 1853. where 11e met and worked under
Prolessor James Syme. This was a particularly happy relationship and. because
Edinburgh was so far ahead ,of London in
Figure 2: 19th cent ury amp utati on saw, knives and muscle retracto rs.
6
surgery, Lister decided to stay. A decision
1I1at was confirmed when. in April 1856,
Lister married Agnes. the eldest daughter
01 JamesSyme. The ceremony was followed
by a three month tour of Europe. during
which lime the medical schools of Belgium.
Germany. Switzerland. Italy and Austria
were visited .
On their return to Edinburgh, Lister began
intenSive research Into the causes and
nature of inflammation and suppuration .
The microbiologist
Joseph Lister became increasingl y dissatisfied with the current theories of the
cause and prevention of surgical se p sis. AI
that lime. putrefaction of organic ma tterwas
conSidered to be a slow oxidation process
and microbes were dismissed as being a
mere consequence of this oxidative change.
If. however. the oxygen in air caused putrefaction, what was the explanation of the
high Incidence of sepsis in surgical wards.
less incidence in medical wards and still
less Incidence in patients nursed at home?
Why should one only, of two wounds in the
same patient. become septic? The epidemiological lacts in the genesis 01 wound
putrefaction seemed to implica te the
atmosphere, though not its constituent
gases. The answer to this problem became
appa rent to Lister after he moved to Glasgow
University in 1860. to take the Chair of
Surgery. It was here that the Professor of
Chemistry (Thomas Anderson) told Lister 01
Louis Pasteur's work on fermentation and
the role of micro-organisms. Lister became
convinced by the germ theory of disease,
although in the early 1860's it was not
generally accepted and would continue to
IS worth recalling that Ignac Semmelweiss
had taken a similar step, 20 years earlier in
1847, when he chose to use chlOride of lime
for the disinfection of the hands of doctors.
students and all nursing staff . Semmelweiss
11ad noticed that his hands. and ti10se of his
colleagues and students, all retained the
smell 01 putrefaction from "the autopsies
carried out on dead patients Chloride of
lime removed this odour. a fact known to
mortuary attendants in Paris, who used the
same compound to soak the sheets in
which they wrapped the dead . Lister and
Semmelwelss faced the same daily ward
round of sepsis, misery and death which
neither man could accept. They were both
men 01 courage and intuitive confidence
and they bOlh knew that bold steps had to
be taken_ It was others who would patiently
tOil at experimental proof and ultimate
Justification
In 1866 Lister could only use the 'guill by
Figure 3: The lister ca rbolic acid spray in action during surge ry.
be disputed by eminent scientists for many
years to corne. Although Pasteur had found
microbes in air, liquids and solids, Lister
decided that air was the chief presumptive
factor In the surgical ward . He recognised
that control of ward or surgery air was
technically impossible. so he took the
obvious step of trying to con trol only the
immed iate environment of the wound. Al l
that was required, he wrote in his 1867
paper, was "to apply the wound wi th some
substance capable of killing these septic
germs, yet not too potent as a caustiC". He
usually Infest cattle fed upon such pastures"
He then deVised a small hand pump which
would continuously produce a fine spray of
dilute carbolic acid Into the air. onto the
hands of the surgeons and the wound in the
patient. Thuswasanllseptic surgery created.
Mucl1 later. in 1890. he reported how his
original concept 01 spraying phenol to
sterilise Ole air was wrong but by that time
the principle 01 antisep tic surgery was well
eSlablished (Figure 3 & 4)
Lister was the son of a distinguished
microscopist and was familiar with the
found Ihal subslance In phenol (carbolic
microscope lrom early youth , He exploited
aCid) HIs choice of this chemical was influenced by an epidemiological consideration. "In the course of the year 1864, I was
mucl, struck wi th an account 01 the remarkable effects produced by carbo lic aCid
upon sewage of the town of Carlisle, the
admixture of a very small proportion not
only preventing all odour from the lands
irrigated With the reluse material but. as it
was stated. destroying the entozoa which
microscopical techniques throughout his
researches and his voluminous notebooks
on bac teria testily to his interests in microbiology. However, the technique of antiseptiC surgery that he had devised had
nothing to do with the study 01 microbes as
such. It was the solution to what Lister probably recognised from the beginning as a
problem in epidemiology. Shoultl Lister have
taken thiS experimentally unproved step? It
association' proollor his antiseptic surgery.
His logic was based on the following
syllogism:
•
•
Putrefaction IS caused by microbes
Wound sepsis is a form of putrefaction
Wound sepsis is caused by microbes.
It was left to Robert Koch and others to
provide the rigorous proof of the theory
wh ich Lister had so rapidly grasped and
acted upon Nevertheless, until such proof
had been overwhelmingly demonstrated,
Lister continually faced bigotry and ignorance from many of his surgical colleagues.
Undaunted by fierce and sometimes vituperatlvecritlcismof his pnncipleo! antiseptic
surgery. Lister was able to report considerable success by 1870 (Lancet i : 4 , 40) but it
did not si lence his critics,
lister returned to Edinburgh in 1869 to
lake over his father-in-Iaw's Chair because
James Syme had retired with ill-health. This
new. more academic apPolOtment, gave
him Inc(~ased time to continue his studies
on bacteria. Among the records of his work
In 1871/72 (On Bacteria In Common Place
Books Vol 1 Royal College 01 Surgeons,
'London pp31 - 170) Lisler nOled thai a
growth of penicillium mould appeared to
inhibit bacteria; this observation was made
some 50 years earlier than Fleming . In 1874
Lister wrote to Pasteur to express his
appreciation 01 the importance 01 Pasteur's
work on hiS own research . This contac t
established a long and cordial friendship
between them.
Return to london
Although Lister was regarded very highly in
Scotland (and widely acclaimed In Europe)
his reputation in London was not high and
his work was regarded with apathy and
contempt. Lister's friends persuaded him to
apply for a Chair in Clinical Surgery at King's
College Hospital. London and he accepted
it in 1877. His studies on bacteriolog y cOheerned the spoiJage of milk and the p utrefaction of urine, which he used as models
lor the role of bacteria in tissue. In attempting to isolate pure cul tures from such infected malenal. lister deVised a micro-dilution
technique which enabled him to isolate
Bacterium lactisfrom milk. Probably the first
liqUid. pure culture technique in the history
Figure 4: Ca rbolic acid spray apparatus.
of baclerlology,
7
PASTEUR
LISTER
KOCH
Louis
Joseph
Robert
born
born
born
1822
1827
1843
I
I
Met together in London 188 1at the 7th International Medica l Congress
I
died
I
I
died
died
1895
1912
1910
(73 years)
(95 years)
(67 years)
Figure 5. The three great micr obio log ists of t he 19th century.
Reports 01 the work 01 Robert Koch , on
the isolation o f bacteria usmg agar plates,
had reac hed Lister and in 1881 he invited
Koch todcmonslrate his tec hnique in King 's
College Hospilal labora lori es This was the
occasion of the 7th International Medical
Congress and Pasteur was present In the
audience. Lister quickly recognised the
superiority of this technlqL.e ove r his own
dilution me thod and freely praised the
:1
:1
younger man's work. as did Pasteur Lister
continued hiS friendship with Koch and
changed his role to one 01 supporting the
works 01 Koch, Pa steur and othe rs, rather
than co ntinuing with his own angina l contn·
butions (Figure 5).
In t 890, Sir Joseph Lister (t1e was made
a baronet In \883) vIsi ted Berlin to briefly
examine Koch 's work on tuberculin and Its
role In the treatment of tuberculOSIs. In spite
01 the brev ity 01 his examination, his highly
suppor tive report (Lancet Dec 13 1890·
1257 1259) was totally uncritical. Like Koch,
Lister desperately wanted this promising
c ure to succeed Perhaps this was one of
the few occaSions when Lister's heart over·
rul ed his head
Lister retired from his p rofessorship at
King's College in 1892, al the age of 65
years In the same year he vlslled Paris to
attend the great ceremony at tile Sorbonne
to honour Pasteur's majOr contributions to
microbiology ove r tile past 25 years (Fi gure
6). The art ist Rixen painted till S well -known
pic ture of Uster mounting the platform to
greet Pasteur With w idely outst retched arms
In 1895 Lister was appointed President
of the Royal Society and In the same year
was created a peer (Ba ron Lister). Other
honours and titles were also bestowed on
him, almost to the end of hi s life in 1912.
Th e Li s ter In st itute
Just as Paris pa id tribute to Pasteur wit h the
erection o f tile famous Pasteur Institute, so
the Ci ty of London fathers decided to honour
Lister by setting up a research centre In
London. Plans were prepared , t60,000was
raised and in July t891, the Li ster Institute
of Preventive Med lcineop ened at the foot of
Chelsea Bridge. At first it wa s not welcomed
by liS nelgl1bours, many of whom saw it as
a breeding ground for germs that might
escape. They were later won over as its
reputation rose and it became a ce ntre o f
medical excellence By 1895, the Institute
was In finanCial difficulties and It was saved
by lhe generous gill of £250,000 from
Edward Cecil Guinness (the first Earl of
Iveagh), The Earl responded to the appeal
because one of his stablemen had, two
years earlier, been bitten by a rabid dog. To
save the man 's life, he was sent to the
Pasteur Institute for treatment. This gift of
life was not forgotten by the Earl. who acknowledged his servant's debt to microbiology by saving the Lister Institute. Donated
money cannot last for eve r and in 1975 the
Lister Instit ute closed because its funds
were exhausted . The buildings and si te were
sold and the money raised was used to
c reate a foundation to provide medical
research funds. Thus the Lister Institute of
Preventive Medicine still exists as an adminIstrative body which annually gives some
£750,000 in resea rch grants throu ghout
Britain .
Ep itogue
Joseph Lister started his distinguished
career as an intelligent and hardworking
surgeon. HIS compassionate concern for
the patients ~nder his care drove him to
es tablish antiseptic surgery. Thi s led him to
furttl er e xploration o f the young science of
microbiology and strong support for the
new ideas coming ou l of Europe. Perhaps
only the hOI-air sterilising oven remains as
hiS life's memento to microbiology but his
lotal cont ribution must be Judged as Pasteur
expressed it in a leIter to Lister in 1874 . "It is
an enigma to me that you can devote you rsel f to researches which demand so much
care. time and incessan t painstaking, at the
same lime as you devote yourself to the
profeSSion of surgery and to that o f the chief
su rgeon to a great hospital. I do not think
IIlat another instance of such a prodigy
could be found amongst us here." "Joseph
Llsler will be remembered for revolutionising
surgery and diminishing rnorlalily. 11 was
eS/lmaled Ihal by Ihe end 01 Ihe 19th
Cerl/ury. Lislers work had saved more
human lives Ihan al/ Ihe wars of that century
had sacrificed."
( Tunes Obituary, February 121h 191 2)
Bibliog raph y
Godlcc. AJ (1924). Lord Llsler Clarendon Press.
Oxford
MllesAA (1967) Brit J Surg 415418
Tile Collec/ed Papers of Josep/J. Baron Lis/er( 1908)
Clarendon Press, Oxford
Front cover picture
The front cover picture from Cu{lure 12.2
showed enhanced pigment production
by Streptococcus agalactiae (Group B)
on Islams medium. The enhancement
was caused by the sulphonam ide disc
which can be seen at the top of the
picture. TechniquecoulesyofDr. M. de la Rosa
Lister mounting the rostrum at the Sorbo nne to embrace Pasteur (1892).
8