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The Evolution of the Five Cardinal Signs of Inflammation: A Historical Perspective, Study notes of Pathology

The history of the five cardinal signs of inflammation, as described in various medical texts from ancient Rome to the modern era. the contributions of Galen, Celsus, and other authors, and the evolution of the signs over time. It also highlights some inconsistencies and errors in the attribution of the signs to specific authors.

What you will learn

  • How did the understanding of the cardinal signs of inflammation evolve over time?
  • Which authors are incorrectly attributed the four cardinal signs of inflammation?
  • Who first described the four cardinal signs of inflammation?
  • What is the meaning of the fifth cardinal sign of inflammation, functio laesa?
  • When did Galen add the fifth cardinal sign of inflammation?

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DISTURBANCE
OF
FUNCTION
(FUNCTIO
LAESA):
THE
LEGENDARY
FIFTH
CARDINAL
SIGN
OF
INFLAMMATION,
ADDED
BY
GALEN
TO
THE
FOUR
CARDINAL
SIGNS
OF
CELSUS
L.
J.
RATHER
Department
of
Pathology
Stanford
University
School
of
Medicine
Stanford,
Calif.
Quid
enim
stultius
quam
incerta
certis
habere,
falsa
pro
veris.
-Cicero
FATUOUS
it
undoubtedly
is,
as
Cicero
says,
to
take
the
uncertain
for
the
certain
and
the
false
for
the
true.
But
we
are
all
liable
to
do
so
at
times.
Karl
Popper
reminded
us
not
long
ago,
in
an
essay
entitled
On
the
Sources
of
Knowledge
and
Ignorance,
that
most
of
what
we
know
or
think
we
know
is
of
traditional
origin,
i.e.,
what
we
have
read
or
have
been
told.'
It
is
doxa
not
epistemj,
opinion
not
knowledge.
The
distinc-
tion
is
apt
to
be
lost
sight
of
with
a
readiness
that
is
inversely
proportional
to
our
real
knowledge
of
the
topic
under
discussion.
The
remark
applies
not
only
to
the
layman
but
to
the
scientist
qua
scientist.
Those
of
us,
for
example,
who
received
our
biological
or
medical
education
in
the
1930's,
1940's,
and
I950's
had
no
doubt
that
the
normal
diploid
number
of
chromosomes
was
48;
those
who
were
educated
in
the
i960's
"know,"
with
equal
conviction,
that
the
real
number
is
46.
Since
we
are
all
in
the
same
boat
here
I
hope
that
no
one
will
suppose
that
in
the
following
paragraphs
it
has
been
my
intent
to
deride
an
often
much
maligned
group
of
purveyors
of
tradition,
the
authors
of
textbooks-specifically,
the
authors
of
textbooks
of
pathology.
Bona
venia
horuin
optimorum
viro-
rum
dixerim-I
speak
without
offense
to
these
best
of
men-as
Cicero
also
said,
more
or
less.
The
matter
that
I
am
about
to
present
does
have
its
comical
aspects,
but
I
hope
that
the
amusement,
such
as
it
is,
will
be
shared
by
those-insofar
as
they
still
survive-at
whom
we
may
smile.
The
fifth
cardinal
sign
of
inflammation,
added
by
Galen
in
the
second
century
A.D.
to
the
Celsian
tetrad-calor,
rubor,
tumor,
and
dolor-of
a
century
and
a
half
earlier,
is,
as
attentive
readers
of
modern
Vol.
47,
No.
3,
March
1971
pf3
pf4
pf5
pf8
pf9
pfa
pfd
pfe
pff
pf12
pf13
pf14

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DISTURBANCE OF FUNCTION

(FUNCTIO LAESA):

THE LEGENDARY FIFTH CARDINAL SIGN

OF INFLAMMATION, ADDED BY GALEN TO

THE FOUR CARDINAL SIGNS OF CELSUS

L. J. RATHER

Department of Pathology Stanford University School of Medicine Stanford, Calif.

Quid enim stultius^ quam incerta

certis habere, falsa pro veris.

-Cicero

FATUOUS it undoubtedly is, as Cicero says, to take the uncertain for

the certain and the false for the true. But we are all liable to do so

at times. Karl Popper reminded us not long ago, in an essay entitled On

the Sources of (^) Knowledge and Ignorance, that most of what we know or think we know is of (^) traditional origin, i.e., what we have read or have

been told.' It is doxa not epistemj, opinion not knowledge. The distinc-

tion is apt to be (^) lost sight of with a readiness that is inversely proportional

to our real knowledge of the topic under discussion. The remark applies

not (^) only to (^) the layman but to the scientist qua scientist. Those of us, for example, who received our biological or medical education in the (^) 1930's, 1940's, and I950's had no doubt that the normal diploid number of

chromosomes was 48; those who were educated in the i960's "know,"

with (^) equal conviction, that the real number is 46. Since we are all in (^) the

same boat here I hope that no one will suppose that in the following

paragraphs it^ has^ been^ my intent to deride an often much maligned group

of purveyors of tradition, the authors of textbooks-specifically, the

authors of textbooks (^) of pathology. Bona venia horuin optimorum viro- rum dixerim-I (^) speak without (^) offense to these best of men-as Cicero also

said, more^ or^ less. The matter that I am about to present does have its

comical aspects, but I hope that the amusement, such as it is, will be

shared by those-insofar as they still survive-at whom we may smile.

The fifth cardinal sign of inflammation, added by Galen in the

second century A.D. to the Celsian (^) tetrad-calor, rubor, tumor, and

dolor-of a century and a half earlier, is, as attentive readers of modern

Vol. (^) 47, No. (^) 3, March 1971

03 4 L. J. RATHER~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

textbooks of (^) pathology know, disturbance of function, functio laesa.

A few examples drawn from textbooks written in English, German,

French, and Italian will (^) suffice to make the point. Lord Florey (1970) tells us that "... the (^) doctrine of the four cardinal signs of in- flammation, redness, swelling, (^) heat and pain, was enunciated by Celsus

.. .and to these Galen. (^).. added a fifth sign Functio laesa." 2 Franz

Buchner (i966) lists rubor, calor, tumor and dolor, and adds, "Galen

annexed thereto fuictio laesa, the disturbance of normal function, as a

fifth cardinal symptom of inflammation."3 Pierre Dustin (i966) calls

Celsus a (^) "Roman patrician who... underlined the four 'cardinal' signs: rubor, tumor, calor, dolor." And "Galen was to add to these signs the notion of impaired (^) function (functio laesa) ."4 Emilio Verrati (1938),

who quoted directly from Celsus, finds that the "clinical manifestations

of inflammation were expressed synthetically by Celsus with the aphoris-

tic comment, 'Notaoe vero inflammationis sunt quatuor: rubor et tumor

cumn calore et dolore'; to these four cardinal symptoms Galen then added

a fifth: functio laesa."

Occasionally the attentive reader of a textbook of pathology receives

a sharp jolt. A footnote to Morton McCutcheon's chapter on inflamma-

tion in Anderson (I966), for (^) example, informs us that "the 'cardinal

signs' of inflammation are redness (rubor), heat (calor), swelling

(tumor), and pain (dolor) (Galen), together with altered function

(laesa functio) (Celsus)."6 The same bouleversement may be found in

the first edition (1932) of (^) William Boyd's Textbook of Pathology: "It

was Galen in the first century A.D. who named the famous 'cardinal

signs' of inflammation as being calor, rubor, tumor and dolor... to

which a fifth was (^) added by Celsus, functio laesa or impaired function."

Celsus' feat was to bemuse Boyd's readers only briefly, for the passage

was quickly monitored and yanked. In the second and all succeeding

editions of the textbook (^) we read that it was "Celsus in the first century

A.D. who... ." etc. Nothing more is said of Galen or the fifth sign.

Contrary to^ what might be supposed this version, or rather inversion,

of the (^) story did not originate with Boyd, as we shall see. It is not only the textbook writer who transmits the apocryphal

Galenic fifth cardinal sign as verity. Robert H. Ebert, in a multiauthored

treatise (i965) on the inflammatory process, lists the four Celsian signs

as usual, and notes (^) that to these Galen "added loss of function as the fifth (^) cardinal sign of inflammation.s In another recent (^) monograph

Bull. N. Y. Acad. Med.

3 0 4 L.^ J.^ RATHER

306 J.^ RATHER

common among writers of the i (^) 9th and early 2oth centuries, and the ascription of the fifth sign now to Galen, now to unnamed "later

writers," suggests that something is amiss. Fifth, a diligent perusal of

mid-i (^) 9th century German textbooks and monographs allows one to observe the legend of the fifth symptom take form in the hands of its several authors. Sixth, it is possible to find a passage in Galen that may very well have led someone to call the fifth sign, functio laesa, into being, although this passage does not deal with inflammation. Finally, Galen could not have consciously added functio laesa to the calor, rubor, tumor

and dolor of Celsus, since neither the tetrad, the name of Celsus nor the

expression "cardinal sign," in reference to inflammation, occur in any of his writings that have been preserved. Before proceeding with the documentation of these points some gen- eral comments are in order. Historians are often guilty of perpetuating mythical or legendary stories. Once established in the literature such fables have the habit of moving from the hands of one writer to another and reproducing themselves (^) from one generation to the next rather in

the manner of an inherited disease, wie eine ewige Krankheit fort, as

Mephistopheles said of the law. Some of the stories are trivial and hardly worth rebutting, others are both important and misleading, still others are almost too good to dispense with even after we have learned that they are false. As G. Kitson Clark recently pointed out, some of them prove to be stories that have merely slipped their historical moor- ings, i.e., the^ evidence^ on^ which^ they were based has been lost. From

time to time such evidence may turn up again, to confound the sceptic."

From the standpoint of the general historian certain of these legends (^) have been commented on (^) recently by that entertaining and witty writer, Robert Birley, in a little monograph entitled The Undergrowth of History.'4 Historians of medicine and science have dealt with the matter

also. "Mistrust is the cardinal virtue of the historian," writes Walter

Artelt, before^ presenting a few^ illustrative cases.'5 One of these is

relatively trivial: the fact that while we do not know the gens name

borne (^) by Galen the one usually ascribed to him, "Claudius," almost cer- tainly stems from^ a^ misinterpretation of the honorific "clarissimus," ab- breviated "cl." Walter von Brunn wrote in 1937 that the absence of any gens name^ for^ Galen^ in the^ manuscript sources had been noted as far back (^) as 1887, and that in (^) 1902 Karl Kalbfleisch and Karl Sudhoff had agreed with respect to the misunderstood abbreviation. The misunder-

Bull. N. Y. Acad. Med.

3 o^6 L.^ J. RATHER

DISTURBANCE 307

standing did not arise until the I5th century, when printed versions of

Galen's works began to appear.16 A more misleading legend, also men-

tioned by Artelt, is that of Albrecht von Haller's I 2,000 book reviews.

Heinrich Rohlfs proved in i 88o that this inherently unbelievable num-

ber was a typographical error for 1,200, itself a startling enough figure

when one recalls the enormous mass of von Haller's other writings, (^) not

to mention his nonliterary activities.18 That both legends still survive

indicates the hardiness of the genus.19 A third legend mentioned (^) by Artelt is also of a kind that is inherently unbelievable, (^) and it (^) perhaps

belongs as well to the category of those too good to forget.20 The

story is that Duke Henry I of Bavaria, desiring to test the medical diagnostic skill of the famed Nothker (^) Pfefferkorn, abbot of (^) St. Gall (^) in the i^ oth century, sent him as his own the urine of a lady's (^) maid. The duke was promptly informed by the abbot of St. Gall that a miracle would soon take place-within a month (^) he would bear a child. And the lady's maid did in fact deliver a child within (^) the month. The modern archivist who brought the story to light took it at face value and con- cluded that the skill of i oth century physicians was not to be scorned. Artelt suggested that had the archivist consulted his (^) family physician he

might have been spared this lapse.22 To an entirely different category

belongs the story of Galileo's experiment (^) at Pisa where, by dropping weights from the Leaning Tower, he is said (^) to have disproved the Aristotelian claim that heavy bodies (^) fall faster than light bodies of the same material and thus (^) demolished Aristotelian physics. This story is

false, misleading, and unfounded in almost every conceivable sense, as

Alexander Koyre showed in (^) 1937, yet it is one that has been told and retold with various embellishments ever since it was loosed on the world

by Viviani.23 The legend that I am here attempting to overthrow

(bearing in mind that such attempts are rarely successful) lies on a scale

of importance somewhere (^) between the relatively trivial-such as Galen's apocryphal gens name-and the really important-such as the legend of

Galileo's experiment at the Leaning Tower.

We return (^) now to the so-called Galenic fifth cardinal sign of inflam-

mation, disturbed function, or functio laesa. The earliest reference to

it that I have been (^) able to find does not, significantly enough, assign it to Galen. Uhle and (^) Wagner, in I 864, after mentioning local heat as the prime symptom of inflammation, (^) have this to say: "Celsus himself placed thereafter the other three (^) cardinal attributes, hence in sum four: calor,

Vol. 47, No. 3, March 1971

DISTURBANCE OF FUNCTION 3 0

DISTURBANCE OF FUNCTION

mode, and is to be found in Martin (I904),36 Adami (I9IO),37 Hewlett

(I912) ,38 and Karsner (1926).39 Ribbert shifted from A to something

approaching y in the 3d edition of his work (i908).

When the fatherless fifth sign, functio laesa, in /8 (in which calor,

rubor, tumor, and dolor are credited to Galen) is assigned to Celsus, we

have version 8. We have already met with 8 in both the first edi-

tion of Boyd (1932) and the latest edition of Anderson ( I 966). A still earlier instance of 8, which is apparently a contribution of the English- speaking peoples, turns up in Muir (I924), who informs us that "Galen gave, as its cardinal signs, tumor, dolor, rubor and calor.... To these Celsus added another of importance, namely functio laesa, or impaired function." Anderson has been less fortunate than Boyd in the matter of editorial attention, and his grotesquely incorrect version-which would have Celsus adding a cardinal sign that was never his to the nonexistent

four cardinal signs of a man who lived a century and a half later-

continues to eke (^) out its existence in a footnote, where it clings to the larger text like some hardy parasite that cannot be dislodged.4" We come now to the version I shall simply refer to as the "canonical," not (^) necessarily because it is the version with which modern readers of textbooks are most familiar, but because it represents the legend in its most (^) fully developed and palatable form. A few examples of the canoni- cal version were presented in the opening paragraphs of this paper.

Celsus, we recall, is in this version credited with the introduction of

color, rubor, tumor, and dolor, and to these Galen is said to have added a fifth cardinal sign, functio laesa, or disturbed function. When was the canonical version introduced? The earliest exhibit in my collection is that of Tendeloo (I91I9), who states: "Celsus himself... grouped

rubor, tumor, calor and dolor together... Galen annexed as a fifth,

functio laesa, disturbed activity."42 It is possible that a still earlier in-

stance of the canonical version exists somewhere, either within the realm of textbook literature or outside of it, for I cannot claim that my search has been exhaustive.

Marchand, who is the only writer to have given the origin of the fifth

symptom any attention, as far (^) as I (^) know, pointed out in 1924 that its

parentage was^ somewhat^ uncertain.43^ Marchand did not differentiate

between the introduction of the fifth symptom, as such, and the intro-

duction of the Latin (^) tag functio laesa. It is rather more curious that he

had nothing to say about the ascription of the fifth sign to Galen. The

Vol. 47, No. 3, March 1971

310 L. J.^ RATHER-

omission would seem to be significant, since he was well acquainted with Galen's views on the symptomatology of inflammation (he quotes them at length) and he did not hesitate to point out that Birch-Hirsch- feld, Ziegler, and others had wrongly assigned the four cardinal symptoms

calor, rubor, tumor, and dolor to Galen. On the face of it the omission

would suggest that the habit of ascribing functio laesa, to Galen was not

yet widespread at the time Marchand wrote.44 What Marchand had to

say on the subject is worth careful reading:

To the old four cardinal symptoms disturbance of function

('Functio laesa') was later annexed in addition as a fifth, yet in

no way with justice, since it is not a phenomenon peculiar to the

inflammatory process, but one inseparable from every disease- state, whether^ or^ not^ this is^ bound^ up with^ an inflammatory

process. Who first gave Functio laesa the meaning of a 'cardinal

symptom' has not been precisely established. The old interchange

of the general process with inflammatory disease underlies this

assumption.

Marchand also called attention to James Macartney who, he wrote, in 1838 mentioned as a "fifth cardinal symptom the alteration or disappear-

ance of normal secretion (thus a functio laesa)."46 (What Macartney

actually wrote^ was that inflammation is characterized by "heat, redness,

tunIour and pain; to which should be added, an alteration or suspension

of the natural secretions of the part";47 he says nothing of Celsus, Galen,

the cardinal signs, or functio laesa). Marchand also noted that Virchow

had emphasized disturbance of function as an important feature of the inflammatory process. He quoted in support of this claim a sentence that had at its (^) beginning a reference to a paper written by Virchow in i852 and at its end a reference to one written in i854; this left the reader to puzzle over the source of the interior, supposedly direct, quota-

tion from Virchow.48 As it turns out the quotation from Virchow is a

chimera made by grafting the middle of one sentence onto the tail of

another (^) written two (^) years later.49 As far as Virchow's beliefs were

concerned, however, Marchand's point was valid and his reference to

Macartney contains another clue to the origin of the fifth cardinal symptom, functio laesa. Virchow's views on inflammation would require our attention if only for the fact that (^) his first (^) paper on (^) the subject appeared in I843 and his

last, 57 years later, in i900.50 In i854, with reference to the question

Bull. N. Y. Acad. Med.

3 I^0 L.^ J.^ RATHER

312 L.^ J.

the ancients do not thus distinguish it; for they called any heat

or inflanunmation a phlegnion, as I have frequently demonstrated.

But from the tinie of Erasistratus it has been customary to term

those tumors phlegmnons, in which there is not only an inflam-

matory heat but also a resistance and pulsation; they have also of

necessity a redness so-called," etc. (Comment. 3 in liber Hippo- crat. de Fracturis. Charter, vol. XII, p. 236). And in like manner

he in another place (De tumoribus praeter naturam cap. 2.

Charter, vol VII, p. 313) mentions heat among the diagnostic

signs of a phlegmon. And thus Aegineta says,^ that^ indeed^ it was usual to call all hot tumours, accompanied^ with pain and^ burning

heat, by the name of^ phlegnions:^ But that even these are said to

differ according to their efficient matter: for good blood, of a moderate consistence, flowing plentifully^ and^ forcibly^ into any part, being there impacted by its quantity occasions the phlegmon properly so called; but yellow bile lodging in any part forms an herpes; and blood flowing together with yellow bile causes an erysipelas: but when the influent blood is very hot and thick it

usually produces carbuncles (Aegineta, liber 4, cap. I7, p. 63.

versa). Heat was therefore a common sign of every inflammation among the ancients, who gave the common appellation of phlegmon to^ all^ kinds^ of^ inflammation;^ but^ they^ afterwards^ re- strained it to that species of inflammation, in which there was a resisting tumour, accompanied with a redness, and a burning

heat; but^ to^ the^ other species^ of^ inflammation^ they^ gave^ different

names. Thus in Celsus (liber 3, cap. IO, p. 139) we read, that the signs of inflammation are four; to wit, a redness and a tumour with heat and pain. Whence it appears, that the general name of inflammation was, even among the Latins, restrained to only one

particular species."

In this passage van Swieten, carefully giving chapter and verse, has

informed us that Galen's phlegmoni is distinguished by swelling, pulsa-

tion, and heat, but that^ the^ "ancients," according to^ Galen, called^ any

hot localized^ lesion^ a^ phlegnonj, until^ Erasistratus^ (who^ lived^ almost five centuries before^ Galen-as^ far^ back from^ him^ as^ Paracelsus^ is^ from

us) limited the term to^ those^ tumors^ or^ swellings in^ which^ not^ only^ heat

was present, but^ resistance, pulsation^ and,^ necessarily,^ redness^ as^ well.

Bull. N,^ Y,^ Acad,^ Med

3 I^2 L.^ J.^ RATHER

DISTURBANCE OF FUNCTION 3 1 3

(In that hardier time pain was perhaps less regarded; one wonders why

our "Roman patrician," Celsus, accorded it such importance.) Com-

menting on the writings of Paul of Aegina (who lived about five centuries after Galen) van Swieten notes that by then the term phlegrnone was applied to all hot tumors with accompanying pain and heat. The various species of inflammation (drawn by "Aigeneta" from

Galen) were also referred to at times as phlegmons, although they were

more properly designated^ erysipelas,^ herpes, and so on. At the close of his note van Swieten refers to the Celsian tetrad and infers that the

"Latins" used the general term inflammation for one particular species.

(The truth is that the "Latins," by and large, never did use the technical term inflammatio mentioned by Celsus as a translation for the Greek

phlegmonj.55) Most important, in all of what van Swieten has to say

there is no reference whatsoever to a Galenic fifth sign, functio laesa,

or disturbance of function. If it is enumeration we desire we can find the signs and symptoms of inflammation up to the number of seven in the Universa medicine of Bartholomew Pardoux (Perdulcis), a i6th century Galenist of Paris. The numbering occurs in the following passage:

Hence many symptoms arise, which distinguish phlegmon from

other tumors. Firstly a prominent swelling (tumor) which in-

volves not only the skin but also the flesh, and this is not diffuse

but gathered and presented in a point; the part only undergoes

distension. Secondly heat (color), which is not great right at the

start but increases in the process of time, perspiration being

checked because of obstruction of the channels, whence it is

followed by festering. Thirdly, redness (rubor), not only as

the companion of heat but also as a sign of the underlying

humour. Fourthly, pulsation (pulsatio), now from the repressed

movement of an artery that is somewhat dilated by the increased

use of the pulse, now by the impulse of fervid matter, especially

when pus is being formed. Fifthly, tension (tensio) which comes

about from^ overfilling. Sixthly, hardness^ (durities) and^ resistance

(renixus), for the same reason. Seventhly, pain (dolor) if the

part is^ sensitive, because^ of^ immoderate^ heat, tension and^ tearing

(ex cap. i, liber (^) I3. Method. et 2. ad Glauco. cap. 2. de Tumorib. et. (^) 5. liber^ 2. de locis^ affectis), in the^ sharpness^ of which^ phleg-

mons exceed other tumors."

Vol. 47, No.^ 3, March 1971

DISTURBANCE OF FUNCTION 3 1 5

Galen disease is a disturbance of physiological function. We (^) may recall that Marchand suggested as a possible explanation of the origin of the

fifth cardinal sign a confusion of inflammation with disease in general,

although he did not follow up his own lead. The close approximation of functio laesa to which I refer is to be found in Galen's well-known

essay on the medical art (Techni latriki, Ars Medica). The same

passage also turns out to be the (^) source of Macartney's "alteration or suspension of the natural secretions of the part," which he suggested in I838 as an addition to heat, redness, swelling, and pain. The (^) context of the passage is as follows. Galen is presenting a wide range of (^) signs and symptoms met with in various diseases. After mentioning dyspnea, cough, pain, and disturbance of phonation as features of diseases of the trachea, he writes: "And in the same way affections of all other parts are diagnosed from swelling, pain, disturbance of functions and (^) difference of excretions. The praeternatural tumors are indeed (^) phlegmons, erysi- pelas, scirrhi and edemata." I-le then briefly comments on the kinds of local change that give rise to pain, and adds (^) that "function, however,

is injured in a threefold manner, weakened, perverted or not carried out

at all."63 The Greek of Galen for the phrase "disturbances of function"

is blabes energei5n, and the translation given in Kuhn is functionum

offensione. The Greek for "function, however, is injured" is blaptetai

de hi energeia, and the translation autem functio laeditur. The conclu-

sion that functio laesa is the illegitimate descendant of functio laeditur

seems irresistible, but the precise (^) circumstances of its birth remain obscure.

The moral of the whole story is perhaps too obvious to need empha-

sis. I shall close with some words borrowed from Alexander Koyre's

essay on Galileo and the experiment at Pisa: Quant a (^) sa morale... nous

en voudra-t-on de laisser aux lecteurs le soin de la tirer eux-mne177es? 64

NOTES AND (^) REFERENCES

  1. Popper, K.: On the Sources of Knowl- edge and Ignorance. In: Conjectures and Refutations, 2d ed. New York, 1965, pp. 3-30.
  2. General Pathology, 4th ed. Lord Florey, ed. London, 1970, p. 22. Another in- stance occurs in Walter and Israel: "The cardinal signs of inflammation- calor, rubor, dolor and tumor,-have

been known (^) since the original descrip- tion (^) by Celsus in the first century A.D.: to these Galen a (^) century later, added a fifth, (^) functio laesa or loss of func- tion: (^) Walter, J. B. and Israel, M. S., General (^) Pathology, 2d ed. London, 1965, pp. 97, 98.

  1. (^) Blichner, F.: Allgemeine (^) Pathologie, 5th ed. Muniich, 1966, "Galen fiigte als.

Vol. 47, No. 3, March 1971

3 I 6 L. J. RATHER

  1. Kardinalsymptom der Entziindung die Functio laesa, die Storung der normalen Funktion, hinzu," p. 398.
  2. Dustin, P.: (^) Lecons d'anatomie patho- logique gtewrale, Brussels 1966,^ p. 293: "Celsius [sic], patricien roman qui... soulignait les quatres signes 'cardinaux': rubor, tumor, dolor, calor. Galen... devait ajouter 'a ces signes la notion de trouble fonctionnel^ (functio^ laesa)."
  3. Verrati, E.: Pathologia Generale,^ 3d ed. Milan, 1938, p. 400:^ "le^ manifesta- zioni cliniche dell' infiammazione acuto furono espresse sinteticamente da^ Celso col noto aforismo, 'Notae^ vero^ inflam- mationis sunt quatuor: rubor et^ tumor cum calore et dolore'; a^ questo quattro sintomi cardinali Galeno ne^ aggiunese poi un quinto: la functio laesa."
  4. Pathology, 5th ed. Anderson, W. A. D., ed. St. Louis, 1966, vol. 1, p. 13. Cf. #41 for other editions of Anderson.
  5. Boyd, W. A Textbook of Pathology. Philadelphia, 1932, p. 28.
  6. Ibid., 2d ed. Philadelphia, 1934, p. 96.
  7. The Inflammatory Process. Zweifach, B.W., Grant, L. and McCluskey, R. J., eds. New York, 1965, p. 5.
  8. Spector, W. G. and Willoughby, D. A.: The Pharmacology of Inflammation. New York, 1968, p. 1.
  9. Gispen, J. G. W.: Is the Origin of our Concept of^ Inflammation^ to^ be^ Found in the Ancient Egyptian Medical Texts? In: Verhandlungen des^ XX.^ Interna- tionalen KCongresses fiir Geschichte der Medizin. Hildesheim 1968, p. 229.
  10. Claudii^ Galeni^ Opera^ Omnia.^ Kiihn,^ C. G., ed. Leipzig, 1821-1833,^20 vols.
  11. Clark, G. K.:^ The^ Critical^ Historian. London, 1967, pp. 49-53.
  12. Birley, R.: The Undergrowth of^ His- tory. General Series G. 30. London, Historical Association, 1955.
  13. Artelt, XV.: Einfihrung in die Medizin- historik. Stuttgart, 1949, p. 129.
  14. Brunn, W.: Darf man Galenos 'Clau- dius' nennen? Ciba Zeitschrift 4/43: 1505, March 1937.
  15. Artelt, op. cit., p. 128.
  16. Rohlfs, H.: Eine literarische Legende. Deutsches Arch. f. Gesch. d. med. u. med. Geographie 3:270-274,^ 1880.^ The typographical error is said by Rohlfs

to have appeared in Blumenbach's Bio- graphie of von Haller in 1785. One year later Blumenbach wrote that von Haller was the author of 1,200 reviews. Rohlfs adduces other evidence in support of his claim.

  1. Garrison, F. H.: An Introduction to the History of Medicine, 4th ed. Philadel- phia, 1929, reprinted 1963, pp. 317-318. Garrison writes that von Haller's "fame as poet and botanist soon^ drew^ him away from his native city to the newly established university at Gottingen, where he remained for seventeen years, teaching all branches of medicine, establishing botanic gardens and churches, writing some 13,000 scientific papers, and incidentally achieving his best experimental work." One wonders whether Garrison's 13,000 scientific papers owe^ something to^ the^ typogra- pher's "12,000 book reviews."
  2. Artelt, op. cit., p. 128.
  3. Kletler, P.: Handbuch der (^) ICulturges- chichte, Kindemann, H., ed. 1. Abtlg., 1934-1939 (Bd. 2), pp. 77, 78.
  4. Artelt. ibid.
  5. Koyre, A.: Galilee et l'expgrience de Pise. A (^) propos d'une (^) legende, in etudes d'histoire de la penseet (^) scientifique. Paris, 1966, pp. 192-201. The essay first appeared in 1937. Viviani's account made its appearance 60 years after the experiment supposedly took place and is the sole historical source, according to Koyre (op. cit., pp. 196, 138). E. B. Krumbhaar, in his history of pathology, is also guilty of spreading the story. He calls functio laesa "a dynamic concept that (^) had been announced (^) by Galen but later forgotten" and^ remarks that the four cardinal signs of^ Celsus, "with^ the Functio laesa added by Galen," nicely summarize the gross changes of^ inflamn- mation (Pathology, New York, 1937, pp. 101, 124).
  6. I^ call the instance of "Cla'dius" Galen relatively trivial because no important conclusions have been drawn from it (and perhaps also because I have been guilty of it myself). But if there had arisen a (^) story to the effect that Galen received the cognomen of Claudius be- cause he stammered or was (^) lame, or

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3 I 8 L. J. RATHER

Symptome (nach Celsus) lauten^ Rubor, Calor, Tumor,^ and Dolor.^ Das^ Merkmal Functio laesa^ ist^ spiter^ hinzugefilgt worden."

  1. Martin, S.: General^ Pathology. Phila- delphia, 1904, pp. 1, 2: The phenomena of inflammation in vertebrates are well expressed in^ the four words rubor^ (red- ness), tumor (swelling), dolor^ (pain), calor (heat) (Celsus). To^ these must be added functio laesa^ or^ dimin- ished function." (The^ peremptory "must" is unique.)
  2. Adami, J.: Principles of Pathology. Philadelphia, 1910, vol., 1 p.^ 413:^ Celsus defined inflammation as^ a^ "condition characterized by 'rubor, tumor,^ calor, dolor'-redness swelling, heat^ and^ pain, -to which definition later^ writers^ added a fifth cardinal symptom, that of 'func- tio laesa'." A slight variation is offered by Bruce D. Fallis: "The cardinal signs of inflammation are, therefore, rubor, calor (skin only), tumor and dolor, as described by Celsus.... Often a fifth sign, functio laesa, or improper function of the inflamed part, is added (Textbook of Pathology. New York, 1964, p. 65).
  3. Hewlett, R. T.: Pathology, General and Special. London, 1912, p. 88: "From the times of Celsus... four cardinal signs and symptoms have been recognized ... to which a fifth was later added, viz. the disturbance of function (functio laesa) in the injured part."
  4. Karsner, H. T.: Human Pathology. Philadelphia, 1926, p. 156: "... Celsus, who pointed out four cardinal signs of the condition, redness, heat, swelling and pain (rubor, calor, tumor, dolor). As a result of later studies, a fifth car- dinal sign, disturbance of function (functio laesa)^ was^ added." The phrase "later studies," which has^ its^ amusing side, may owe^ something^ to^ Ribbert.
  5. Ribbert, op. cit., 3d. ed. Leipzig, 1908, p. 168: "Sie wurden bereits von Galen aufgestellt" was somewhat grudgingly altered to "Sie wurden bereits von Celsus und Galen aufgestellt." The fifth sign was^ then^ ascribed^ to^ a^ "spitere Zeit" (as in Thoma) instead of a "neuere Zeit."
  6. Muir, R.:^ Textbook^ of^ Pathology. Phila- delphia, 1925, (^) p. 88. The first printing of the 4th^ ed.^ (1961)^ of^ Anderson's Pathology carried version 8. The 'canon- ical' version appears^ in^ the second^ print- ing of the 4th ed. (1961). The 5th ed. (1966) reverts to (^) S. The five versions do not exhaust^ actuality.^ Another possi- bility that has not been overlooked is to assign all five signs to Celsus, as^ Erich Letterer seems to have done: "... mit den historischen Entzundungszeichen des Celsus: Rubor, Calor, Tumor, sowie mit dem Dolor und der Functio laesa hin- reichend charakterisiert" (A llgemeine Pathologie, Stuttgart 1959, p. 677), al- though the phrasing is ambiguous. The five signs may be listed without men- tioning either Celsus or Galen: "Clinic- ally acute inflammations... are char- acterized by the five cardinal signs: calor, rubor, tumor, dolor and functio laesa" (Sir Roy Cameron in Robbins' Pathology, 3d. ed. Philadelphia, 1967, p. 33). The same occurs in Delafield and Prudden: "The^ concept^ of^ inflammation was originally a clinical one in which the (^) process was marked by special symptoms-redness, heat,^ swelling and pain, and impaired function" (A Text- book of Pathology, 10th ed. New York, 1934, p. 81). Certain other writers men- tion both men but do not^ distribute credits (the^ 3rd^ ed. of^ Ribbert,^ op.^ cit., really belongs in this category): ". die vier Celsus-Galenschen Kardinal- symptome wahrnehmbar sind;^ dazu kommt Functio laesa" (Gotthold^ Herx- heimer's Grundlagen der pathologischen Anatomie, Munich, 1921,^ p.^ 52),^ and Horst Oertel's "from the time of Celsus and Galenus, the most prominent and evident vascular phenomena, the red- dening-the swelling, the heat and the pain (rubor, tumor, calor, dolor) were the cardinal symptoms of inflammation, and to these was later added impaired function (functio laesa)" (Outlines of Pathology, Montreal 1927, p. 236; Oertel adds in a footnote that neither Celsus nor Galen originated the cardinal signs and cites Marchand's Handbuch article, referred to later in this paper). Some writers mention only the four

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DISTURBANCE OF FUNCTION 3 I 9

Celsian cardinal signs, e.g., Boyd, in all editions since the unlucky 1st. A late 19th century example of that formula may be found in Joseph Frank (^) Payne, a Galen scholar: "Numerous definitions have been given. That of Celsus was at one time familiar to all medical stu- dents, but in the present day may have to be quoted: 'The marks of inflamma- tion are four; redness^ and^ swelling with heat and pain"' (A Manual of General Pathology. Philadelphia, 1888, p. 80). Ludwig Heilmeyer and Hans Joachim Kahler combine an evasive manoeuvre with some bad history; after stating that redness and heat were the out- standing symptoms of inflammation for the "Hippocratic physicians," they con- tinue: "Later physicans, as Celsus ( B.C.) Galen (129-201 A.D.) and John Hunter (^) (1794) annexed to rubor and calor, the already named features of inflammation, as further cardinal symp- toms, tumor, dolor, and functio laesa, in addition." (Die Entzitndung und ihre Steuerung. Basel and Stuttgart, 1962, p. 7.) Authors sabotaged by the type-setter deserve a category of their own. Rous- sy's "Note vero inflammationis.^. etc. (Roussy, G. Leroux, R. and Ober- ling, C.: Precis d'anatomie pathologique, 3d ed. Paris, 1950, p. 72) is pedestrian, but Domenico Campanacci's "rubor, tumor, calor, dolor et functio laesa" (note also the spurious 'et') shows im- agination (Inflammation. Proceedings of an International Symposium, Int. Con- gress series No. 163. New York, Ex- cerpta Medica, 1968, p.^ vii.).^ McFar- land's "dolor, color, rubor cum tumor": misplaces the "cum" and scorns the abla- tive ending but the typographical error gives it a nice ring. (A Textbook of Pathology. Philadelphia, 1904, p. 308); Morehead's "functio lessa" (Humbau Pathology. An Introduction to Medi- cine. New York, 1965, p. 101) is rather apt.

  1. Tendeloo., N. Ph.: Allgemeine Path- ologie. Berlin, 1919, p. 334. Where Uhle and Wagner (1864) wrote "Schon Celsus stellte noch... ." etc., Tendeloo put "Schon Celsus... stellte zusam-

menl," which suggests that he was copy- ing (I have translated the troublesome 'schon' as 'himself'). More copying sug- gests itself when Stricker (1883), Rib- bert (199)5, 1908), and Tendeloo all use the verb hinzufigen (annex). The same verb was used by Buchner in 1966 (cf. No. 3). It will turn up again in Bier; cf. No. 47.

  1. Handbuch der allgemeinen Pathologie, Krehl, L. and Marchand, F., eds. Leip- zig, 1924, 4ter Bd., Iste Abt., pp. 78- 469 (contributed by Marchand on the topic of inflammation and containing an historical account of the concept, pp. 89-10()).
  2. Ibid, p. 90. Marchand names Schmaus and Schade among those who have wrongly ascribed the four cardinal signs, calor, rubor, tumor, and dolor to Galen and states that the name of Celsus is nowhere to be found in the corpus of Galen's writings. Marchand cites Tendeloo's Allgemeine (^) Pathologie on p. 102. He either overlooked what Tendeloo had done or had reason for not mentioning it.
  3. Ibid., p. 104.
  4. Ibid.
  5. Macartney, J.: A Treatise of Inflamma- tion. London, 1838, p. 10. Another varia- tion on the theme of the fifth symptom was played by Augustus Bier not long ago. After citing several Galenic defini- tions of inflammation and mentioning the four cardinal (^) signs of (^) Celsus, Bier promises that he will (^) have something to say later of the "fifth cardinal symptom of functio laesa that was later annexed in addition." (^) (He does not ascribe the fifth (^) sign to (^) Galen.) The only further reference to (^) functio laesa that I have been able to find in his long paper is the conclusion that "the acutely inflamed bodily part accomplishes not less but rather more than the normal, and that one should therefore really not speak of a functio laesa, but of a functio mutata of the inflamed bodily part" (Die Entziindung, Arch. f. Klin. Chirurgie 176: 407-549, 1933; cf. pp. 417, 456, 506). Still another is the following: "For cen- turies, inflammation was known as the condition characterized by the presence

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DISTURBANCE OF FUNCTION 3 2 I

with the collaboration of Drennan, A. M.: A Textbook of (^) Pathology, 5th (^) ed. New York, 1948, (^) p. 17. The 1st. (1908), 2d. (1921), and 3d. (1926) editions do not mention the cardinal signs at all. I have not seen the 4th edition.

  1. Fernel, J.: Universa medicina, 6th ed. Frankfurt, 1607. Fernel uses the term "phlegmone" to signify, specifically, a hot, red, praeternatural (^) tumor. It is true that (^) the word inflammatio turns up in his (^) text-"calor quoque ex in- flammatione vehemens quasi pars ura- tur"-but it^ is not used as a technical term and is not listed in the (^) index.
  2. Brissot, P. (^) Apologetica disceptatio, Paris 1622. Like Fernel, Brissot uses the technical term "phlegmonC" instead of (^) "inflammatio." He writes (p. 65): "The disease with which we are con- cerned (^) is phlegmon, the essence of which is made up by the following: an overabundance of hot blood in a par- ticular part, from this hot blood its in- temperature and swelling, then a solu- tion of continuity due to the excessive- ly (^) swelling and pressing tumor, but from (^) the heat and the solution of con- tinuity pain, unless the part is wholly inaccessible to sense."
  3. De Chauliac, G.: Chirvrgia magna Gvi- donis de Gavliaco. Lyon, 1585. In this connection Guy refers to Avicenna, Haly Abbas, Peter of Abano and Ga- len, among others (never to Celsus). He uses the technical term "apostema" in- stead of "phlegmonC" as the name of the genus: "Apostema est tumor praeter naturam... Apostematum multae sunt species" (p. 50).
  4. Celsus states that when blood arrives in vessel,; that are meant for the trans- mission of "spirit" it arouses "inflamma- tionem quam Graeci phlegmonen nom- inant" (De Medicina. Spencer, W. G., transi. (^) London, Loeb Classical Library, 1948, pp. 10, 11). For the next fifteen hundred years, (^) however, the technical medical use (^) of "inflammatio" or "in- flammare" was uncommon. Neither Du Cange nor^ Niemeyer, to name the two chief (^) dictionaries of medieval Latin, gives the technical meaning. It is not to be found in Alexander Souter's Glos-

sary of^ Later^ Latin^ to 600^ A.D.^ (Ox- ford, 1949) or in Wagner's Lexicon Latinum (Bruges, 1878). The 13th cen- tury lexicon of (^) medical terms composed by Jean de Saint-Amand lists (^) apostema and flegmon for aspects of (^) what we now call (^) "inflammation" (Die Concordanciae des Johannes de Sancto (^) Amando. Pagel, J. L., ed. Berlin, 1894). Although the verb "inflammo" occurs in the text (cf. p. 178, op. cit.), it is not used as a technical term. Among the early printed Latin dictionaries neither the first edi- tion of (Robert) Stephanus (Paris

  1. nor Cooper (London, 1580) lists the technical meaning. Henricus Steph- anus (son of the above Stephanus), who compiled a dictionary of medical terms, gives citations from Galen, Aegina, and Actuarius in connection with the term phlegmong and writes that "nostri in- flaminationes, Graeci phlegmonas ap- pellare consuevit" (Dictionariwum medi- cum, 1564). A later edition of Robert Stephanus' Latin dictionary (Lyons,
  2. does give the technical medical meaning of "inflammatio," with cita- tions from both Celsus and Pliny.
  1. Claudii Galeni Opera Omnia, op. cit., vol. 1, p. 357. The Greek version reads (in transliteration) as follows: "ana- logon de kapi ton allon morion (^) hapaln- ton eks onkou, kai ondynes, kai blabi~s energeihn, eti te tes t6n (^) ekkrinomenon diaphoras hai^ diagn6scis esontai, onkous uien dOe (^) tous para physin en phlegnmo- nais, kai erysipelasi, kai skirrhois, kai oidemasin (^) eksetasteon.. blaptetai de hlO energeia trichos, e arrhostos, e plem- nielos, e med' holos gignomene." The early 17th century translation (^) by Char- tier reads: "Eadem ratione aliarum omnium partium affectus ex tumore, do- lore, functionum offensione et excre- mentorum differentia diagnoscuntur. Tumores quidem praeter naturam sunt inflammationes, scirrhi et oedemata (^)... trifariam autem functio (^) laeditur. Aut enim imbecilliter, aut (^) depravate, aut oninino non editur." (In the Latin ver- sion "erysipelasi" has fallen (^) out.) A straightforward definition of disease as a)imornlal diathesis with disturbance of function, and of^ health as normal dia-

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3 2 2 L. J. RATHER

thesis with effective function may be found in Galen, op. cit. vol. VI, p. 21: ".. .ut sit nimirum sanitas affectus secundum naturam actionem perficiens, contra morbus affectio praeter naturam actionem laedens." The Greek reads:

".h.. h6s einai ten hygieian diatlhesini kata poiftikEn energeias, ten de noson diathesin para physin cnergeias blap- tiken."

  1. Koyr6, op. cit., p. 201.

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