1077
Schonlein (1840) in human dermatitides. Henle3 made his
Dogma Disputed
LIMITATIONS OF THE GERM THEORY
G. T. STEWART
M.D., B.Sc. Glasg., F.C.Path.
PROFESSOR OF EPIDEMIOLOGY AND PATHOLOGY, SCHOOLS OF PUBLIC
HEALTH AND MEDICINE, UNIVERSITY OF NORTH CAROLINA, CHAPEL HILL,
NORTH CAROLINA, U.S.A.
The
germ theory of disease—infectious
Summary disease is primarily caused by transmission
of an organism from one host to another—is a gross
oversimplification. It accords with the basic facts that
infection without an organism is impossible and that
transmissible organisms can cause disease; but it does not
explain the exceptions and anomalies. The germ theory
has become a dogma because it neglects the many other
factors which have a part to play in deciding whether the
host/germ/environment complex is to lead to infection.
Among these are susceptibility, genetic constitution,
behaviour, and socioeconomic determinants.
INTRODUCTION
DoGMAS comfortable things which, like favourite
are
armchairs, increase in appeal as time passes. If accepted
uncritically, any theory tends to become a dogma, that
is to say, it becomes the captive of its own postulates. The
more rigid the postulates, the more complete the captivity.
The germ theory of disease is a dogma in so far as it
asserts unconditionally that infectious disease is primarily
caused by microorganisms which are transmissible from
one host to another. The dogma lies in the generalisation
and the elaboration of postulates; the basic fact, that
transmissible microorganisms can cause disease, has been
proved again and again. But a theory, to be valid as a
continuing vehicle for thought, must provide for excep-
tions, must convincingly explain anomalies, must have
embodied in its fabrication a recognition of its limitation
as well as of its extent. A theory lacking in these qualities
is vulnerable at any point to disproof; one which seeks to
maintain validity in the face of anomalies or in contra-
diction to new facts, becomes a dogma. Because it has
never been restated in the light of further knowledge and,
indeed, self-evident truths about infectious disease, the
germ theory must now be classed as a dogma.
EVOLUTION OF THE GERM THEORY
The germ theory has no single author and no clear point
of origin. Social and legislative codes in all the older
civilisations recognised the menace of transmissible
diseases. The notion that a syndrome-specific com-
municable agent might account for epidemics was first
conceived by that most versatile of Venetians, Fracas-
toro, about 1540,1 from observations made descriptively,
even poetically, about syphilis and foot-and-mouth
disease. The contributory concept of specificity of agent
and disease, recognised but not formulated by Fracas-
toro or his followers, was enunciated by Bretonneau2
using as evidence not only clinical and epidemic character-
istics but also pathological changes indicative of portals of
entry of the, as yet unknown, agents of infection.
In 1825 Barthelemy inoculated necrotic material from a
sheep with anthrax into another sheep, reproducing the disease.
]3assi, in 1836, described fungal disease in the silk-worm, and
1. Fracastoro, G. De Contagione. Florence, 1546.
2. Bretonneau, P. Des inflammation speciales. Paris, 1826.
famous deductions a few years later, recognising the com-
municability of infections, together with basic notions such as
the incubation period, portals of entry, immunity, and dis-
infection. In equating miasma with contagion, he reconciled
the neo-experimental with the classical approach; disease arose,
not from infectious material (e.g., chickenpox) per se but from
contagion, implying some form of effective contact. Budd,44
describing the fever at the Clergy Orphan Asylum, drew
attention to all the essential features of typhoid, including the
infectivity of the faeces and the possibility of disinfection of an
agent in water and sewers by chloride of lime. Thus, long before
the identification of pathogenic bacteria, the essential hypo-
thesis of the germ theory had begun to figure in medical,
scientific, and to a very limited extent in general cultural
thinking. It was, nevertheless intellectually unacceptable to
the majority of physicians since it was superficially in conflict
with the hippocratean concept that infectious disease arose
from atmospheric conditions. This and other classical dogmas,
dating from Galen and Arabic medicine, still formed the core,
along with anatomical pathology, of all medical teaching. But
it is important to realise that before the work of Pasteur and
Koch, the issue between pro and contra had begun to declare
itself. Realisation that susceptibility to disease, contagious or
otherwise, lay largely in the host, was part of classical thinking:
the challenge lay in the postulate that a living extrinsic agent
was also involved and, increasingly, the question became
polarised between these viewpoints with surprisingly little
awareness that they were far from being irreconcilable. Mean-
while, even those who, like Virchow5 and Snow,6 perceived
the influence, in epidemics, of environmental and demographic
factors, failed to effect ideological fusion between the reactionary
majority and the avant-garde dissenters whose arguments were,
so far, circumstantial.
When fundamental proof that extrinsic agents could cause
disease in healthy hosts came from the experiments of Pasteur
and Koch in a series of overlapping observations the medical
world, in a remarkably brief period, consolidated the germ
theory with the doctrine of specific astiology which Dubos has
"
described as the most powerful single force in the develop-
ments of medicine during the past century ". Thus fortified,
the theory offered a comprehensive and satisfying explanation
of many forms of disease: it accounted for contagion and
epidemics; it unified varying syndromes such as scrofula,
consumption, and spinal caries into a single disease, tuber-
culosis ; it fitted well with current concepts of evolution and
survival; and it pointed to possibilities of rational prevention
and control. It was the biological equivalent of the economic
determinism of Marx and Engels, and of the mechanical deter-
minism of Kelvin and Faraday, each of which contributed,
provocatively, but profoundly, to the spread of radical
rationalism. Mankind collectively always welcomes simplified
and unitarian explanations of complex happenings: the germ
theory was one of the greatest of all scientific simplifications.
With enlightened opinion already alerted by Bretonneau,
Henle, Semmelweis, and Snow among others, and with
persuasive, powerful minds like Pasteur, Koch, and Lister as
protagonists, the Germ theory swept through medical science
and philosophy like a forest fire-with an equally destruction
effect upon the dead wood. Short-lived, though vehement,
opposition came only from those who resented changes in
established practice, or who objected to the sudden burst of
incontrovertible facts into sanctuaries of privileged opinion,
This reaction, which is a constant attribute of all established
societies, is to be expected and is now operating in favour of,
instead of against, the germ theory. Medical teaching,
diagnosis, and treatment lean heavily upon the prerequisite
that, for every disease, there is a single ascertainable cause; the
3. Henle, J. Reprinted in Bull. Inst. Hist. Med. Johns Hopkins Univ. 1838,
6, 907.
4. Budd, W. Lancet, 1856, ii, 617.
5. Virchow, R. Report on Typhus in Upper Silesia. 1818.
6. Snow, J. On the Mode of Communication of Cholera. London, 1855.
(Reprinted) Commonwealth Fund, New York.
7. Dubos, R. Man Adapting. New Haven, Connecticut, 1965.
1078

object of most research is to identify this cause, and by pre-

vention or treatment to eliminate it. Thus, our approach to
infectious disease is often exclusively germ-oriented, with
vaccines and chemotherapy as the principal weapon of attack.
The fact that these weapons have been strikingly successful in
countless situations supports this attitude but does not neces-
sarily mean that no other attitude is justifiable. The question
confronting us is now whether, by accepting the germ theory
as the main explanation of infectious disease, we are overlook-
ing other determinants of equal or greater importance.
EVIDENCE FOR AND AGAINST

Apart from the historical observations and trends

mentioned above, evidence in favour of the germ theory
comes from four main sources: (a) Koch’s postulates;

(b) the communicability of infection; (c) the spread of

infection (i.e., epidemics); and (d) the efficacy of anti-
microbial agents and procedures (e.g., antibiotics, anti-
bodies, vaccines, antisepsis, sterilisation, asepsis).
Koch’s Postulates .

The basic reasoning of the theory lies in Koch’s four

postulates, all of which are upheld by evidence in some
diseases and some of which are upheld in all diseases.
Framed to differentiate pathogen from non-pathogen,
and to show that a bacterium isolated from a lesion was in
fact the one causing disease, they served and continue to
serve as an exacting standard for microbiologists. Briefly
restated, the postulates require a given pathogenic germ
shall be:
(1) Invariably associated with a given disease. This is
incontrovertible in so far as there is no tuberculosis with-
out the tubercle bacillus, no syphilis without Treponema
pallidum, no poliomyelitis without poliovirus. But the
reverse reasoning is, as often as not, inadmissible: polio-
virus can be carried for months without signs of disease,
as can other enteroviruses, pneumococci, streptococci,
and many other organisms, each of which, in particular
instances, can otherwise completely fulfil the postulate.
(2) Isolated in pure culture from the characteristic lesion
of the disease. This is true if the disease is labelled
exclusively in terms of the actual or expected isolate, and
therefore holds, for example, for gonorrhrea, anthrax,
tuberculosis. If the lesion and syndrome (e.g., pneu-
monia) are taken as a dependent variable, the organism
becomes an independent variable (e.g., pneumococcus,
mycoplasma, various viruses) which may be of equal or
greater prevalence in persons without the disease; in
most hospitals, for instance, the carrier-rate of pathogenic
staphylococci far exceeds the morbidity-rate; in northern
populations, the prevalence of penumococci in winter far
exceeds that of lobar pneumonia.
(3) Able to reproduce the disease when inoculated into
animals. This depends upon the species of organism and
animal. Tubercle bacilli cause tuberculous caseation in
guineapigs, monkeys, dogs, and rabbits but not in mice or
rats. The resulting disease, is, in fact, determined by the
host rather than the bacillus (Mycobacterium tuberculosis)
even in the case of this predictable organism around which
Koch framed his postulates :
With the majority of organisms, including most viruses,
this postulate simply cannot be fulfilled even when
massive inocula, grotesquely different from natural
circumstances of infection, are used.
(4) Reisolated in pure culture from the experimental
lesion. This is a corollary of (3), not an independent
property: if a lesion identical to the original lesion is pro-
duced in the experimentally-infected animal, the organism
will be reisolated; otherwise, it will not except if it
happens to survive passively.
The postulates are, therefore, not basically wrong but
seriously incomplete. They fail to allow for biological
variation and they make no allowance for the complex
conditions influencing infection in natural settings (see
figure); they are narrowly adapted to defining rigid condi-
tions which happen to fit the behaviour of a few micro-
organisms studied on limited lines by Koch and others in
a few susceptible hosts; but from this narrow basis, the
postulates were stretched to form a theory with a general
applicability to all infectious diseases.
COMMUNICABILITY AND SPREAD OF INFECTION
Under these headings the case for the germ is super-
ficially incontrovertible; practically all infections from the
common cold to smallpox are communicable if conditions
for transmission and reception and spread are favourable to
the microbe.8 But, as anyone who has tried to trace or
transmit natural infection knows, communicability varies
with inoculum size,9 donor and recipient,lO and with
many environmental conditions..’ 12 When outbreak
arises from an infected person, the number of susceptible
individuals who will become infected is given by the
equation: -ds=&bgr; i s dt,13 where i is the number of
infectives,s is the number of susceptibles, and a13 the
contact-rate over time dt. In infections spreading from
human carriers in an enclosed community of s+i persons,
there are no factors other than the variables and constants
of this basic mathematical model sinces excludes indi-
8. Burnet, F. M. Natural History of Infectious Diseases. London, 1962.
9. Meynell, G. G., Meynell, E. W. J. Hyg. Camb. 1958, 56, 323.
10. Douglas, R. G., Cate, T. R., Gebone, P. J., Couch, R. B. Am. Rev. resp.
Dis. 1966, 94, 150.
11. Williams, R. E. O. Am. Rev. Microbial. 1960, 14, 43.
12. Sherris, J. C., Lancaster, L. J. J. chron. Dis. 1962, 15, 743.
13. Bailey, N. T. J. The Mathematical Theory of Epidemics. London.
1957.

viduals who are immune because of previous infection,
vaccination, chemoprophylaxis, or personal attributes
while P, the contact-rate, includes the contact intensity
between individuals and other environmental components
affecting infectivity of the germ. The rate of change in the
number of susceptibles, ds/dt, is therefore - (3 s i. If
y=the rate of removal of infectious persons by recovery,
isolation, departure, or death, then the change in the
number of infectives, di/dt, is (3s i-yi. At the beginning
of an outbreak of infection immediately before equilibrium
conditions are altered, di/dt is zero, sos is y/P and i is V-1y,
where is the rate at which new susceptibles enter the
community so that: ds/dt = (3s i + tL = 0. It follows that
the generation of an epidemic is governed by factors which
can be measured, or derived mathematically, concerning
not only the germ but also, and principally, the exposed
population; the attributes of the germ (infectivity, incuba-
tion, multiplication) are included along with environ-
mental, behavioural, and other factors,-’ less easily
measured, in P. If the natural infection is viewed as a
chain of eight events (see figure), the primary factors
governing both development and suppression of infection
can be identified with these parameters.
The chain of events begins with a germ, usually
described in terms which may or may not fulfil Koch’s
postulates as a pathogen to distinguish it from all other
microorganisms. But what is a pathogen ? If it is defined
etymologically as any microbe capable of causing disease,
a range of organisms which are habitually harmless has to
be included; if at the other extreme, the definition is
restricted to those microbes which invariably cause disease
and are never harmless, few if any can qualify since most
disease-producing organisms can be isolated at times from
healthy persons. The true definition must therefore
provide for a chance or conditional element (P and y) and
all pathogens are to that extent facultative. The higher
the value of y and the lower the value of P, the more
must the explanation of disease be sought in factors out-
side the germ-i.e., in attributes of the host, the com-
munity to which he belongs, and the environment in
which he lives. Even highly communicable organisms,
such as influenza and smallpox viruses, Pasteurella pestis,
and Vibrio cholerae seldom produce 100% attack-rates as
judged by morbidity. Indeed, few species of organisms
inoculated directly into the body invariably cause infection
as do venereal disease and vaccination, and even then
the pattern of response varies considerably.
The Efficacy of Antimicrobial Measures
This provides indisputable proof that the germ is the
starting point of infection but not that it is an exclusive or
even principal cause of disease. Theobald Smith’s well-
know equation could be rewritten:
Since virulence is in itself a function of severity and there-
fore not an independent variable, the effect of antimi-
crobial measures may be viewed either as a decrease in the
numerator (chemoprophylaxis or therapy) or an increase
in the denominator (vaccination, serotherapy) whereby
physiological defences are better able to neutralise the
germ at points 4, 5, 6, 7, and 8 in the figure. The same
considerations apply to mass immunisation and chemo-
prophylaxis the effect of which depends primarily upon
interference with the exponential multiplication of the
germ which determines the incubation period between
1079
infection and overt disease.14 Disappearance of the
organism during natural recovery ( "wo die Krankheit zum
Stillsand kommt ") was used by Koch as a corollary to his
first postulate; but, just as an organism can be present
in the respiratory or alimentary tracts without causing
disease, so also recovery can occur, spontaneously or
under therapy, without the organism being eliminated.
Cure, like resistance, depends upon the balance of power.
INTERACTION BETWEEN DETERMINANTS OF INFECTION
If two susceptible subjects are exposed to equal doses
of the same germ and one develops infection while the
other does not, the factor governing the development of
infection clearly lies outside the germ. But the measure-
ment of these governing factors is usually very difficult
for, whereas the germ can usually be isolated and, under
experimental conditions, enumerated with precision, the
extraneous factors tend to be of a nature which precludes
comparable quantitative assessment. It is, however,
possible at least to identify many of these factors, and it is
the task of epidemiology to find other methods of assess-
ing with precision their contribution to infectious disease.
This task can be approached by considering again the
basic model of all infectious situations-i.e., infective
source or subject (i), susceptible host or community (s),
contact-rate (&bgr;), and duration of exposure (dt). If for
the moment we regard the infective source or subject (i)
as germ-linked, then our problem is to define the com-
ponents of susceptibility, contact and time which con-
tribute to the net attack-rate.
SUSCEPTIBILITY
of host, human or animal, has been
Susceptibility a
well studied qualitatively. It is common knowledge that
some subjects are more susceptible to infectious disease
than others, and argument is superfluous. Defining
what is meant by susceptibility is another matter, and
this is where evidence accruing from natural and planned
experiments is necessary. In clinical circles, natural
experiments in this regard are now part of standard
theory. The use of immunosuppressive and cytotoxic
drugs for grafts and transplants as well as for malignancy
and various cryptic disorders, has already yielded (and
continues to yield, increasingly) overwhelming evidence
that if defensive physiological responses are suppressed
practically any organism can produce severe infection,
whether or not it is classified as a pathogen. It is now
well recognised, and a matter of concern, that com-
mensal coliforms, diphtheroids, and yeasts, cause endo-
S
genous infection in this way.15
The use of immunosuppressive drugs in this respect
points to a manner in which susceptibility can be speci-
fically heightened but there are many other, less specific
ways in which the same end result occurs on account
of genetic and metabolic defects or certain, though by
17
no means all, nutritional deficiencies.16 Immunity is
also dependent upon the competitive microflora of the
body, alterations in which can open portals to both endo-
genous and exogenous infection 1g; this can happen
when people or animals are transferred from one environ-
ment to another (" shipping fever ") 19 or as a result of
14. William, T. Jl R. stat. Soc. 1965, 27, 338.
15. Simon, H. J. Attenuated Infections. Philadelphia, 1960.
16. Dubos, R., Schaedler, R. W. J. Pediat. 1959, 55, 1.
17. Scrimshaw, N. S., Taylor, C. E., Gordon, J. E. Am. J. med. Sci. 1959,
237, 367.
18. Dineen, P. J. infect. Dis. 1961, 109, 280.
19. Williams, L. P., Newell, K. American Public Health Association
Conference, San Francisco, November, 1966.
1080
changes in diet or antibiotic treatment. 20 Experimentally,
such changes can be measured and have been proved
again and again to be of prime importance; under natural
conditions, the result of these continuously operating
short-term effects is to produce a change in the whole
pattern of infection with increasing emphasis upon
endogenous factors which are largely man-made in origin.
GENETIC CONSTITUTION
The importance of certain genetic characters as important,
often dominant, determinants of susceptibility (or resistance) is
most clearly shown by species differences in response to
Within species, experimental
common germs (see above).
evidence shows very clearly that the effect of a standard
inoculum of tubercle bacilli 21 or salmonella 22 varies widely
according to arbitrarily selected phenotypic traits. In human
populations, these genetic influences are proved only when
differences in incidence or severity of the major exogenous
infections are observed in their geographic 23 and ethnic
settings.24 In this respect, survival of the less susceptible, if
not of the fittest, is probably a darwinian factor of continuing
importance in evolutionary history but one which is influenced
also by behavioural, social, and economic patterns affecting the
susceptibility of individuals within communities as well as of
communities as a whole. The paramount importance of the
genetic factor is well shown by studies in twins.25 A homo-
zygotic twin has 3 chances out of 4, but a heterozygotic twin
only 1 chance in 3, of developing tuberculosis if the other twin
has clinical tuberculosis. In the United’States, tuberculosis,
pneumonia, rheumatic fever, and infections causing neonatal
death are strikingly
more""prevalentand more severe in
Negroes than in Whites, even when allowance is made for
socioeconomic differences 2s-2s; among the Whites, there is
some evidence that ethnic origin and place of birth also
influences susceptibility.26-28 The evaluation of the genetic
factor in human susceptibility is rendered difficult by inter-
actions with selective evolutionary, cultural, and socio-
economic factors. Evidence for the genetic factor rests there-
fore mainly on analogics in animal experiments, which seem to
show conclusively 29 that, when age, weight, sex, and diet are
controlled, susceptibility and resistance are uniform in groups
which are genetically homogeneous and variable when there is
heterogeneity.
BEHAVIOUR
The convincing examples of how behaviour influences
most
susceptibility of individuals are apparent in everyday experi-
ence : mouth-breathers, nose-pickers, and heavy smokers are
more prone to respiratory infections than those who do not
adopt or who relinquish these habits. Similarly, scratching,
excessive toiletry, and other self-abuses open doorways to skin
infection by lowering local tissue barriers. Sexual promiscuity
increases enormously the chance of contracting venereal disease
just as eating habitually in unsanitary premises increases the
likelihood of diarrhoeal disease, in both instances by raising p,
the contact-rate. In so far as the community is a collection of
individuals, susceptibility to infection (s) is therefore the sum
total of behaviour: if behaviour is altered, in the examples cited,
the germ is almost impotent. Public health programmes which
aim at eradicating, say, syphilis, by controlling only the germ
T. pallidum, because of its unfailing sensitivity to penicillin, are
doomed to failure because of failure to control the prime
determinant, which is human behaviour.
The above examples are crude, but real. More speculatively,
20. Berntsen, C. A., McDermott, W. New Engl. med. J. 1960, 262, 637.
21. Stewart, G. T., Tamorgo-Sauchez, M. J. Hyg., Camb. 1952, 50, 37.
22. Miller, C. P., Bohnhoff, F. J. infect. Dis. 1962, 111, 107.
23. May, J. M. The Ecology of Human Disease. New York, 1958.
24. Coon, C. S. The Living Races of Man. New York, 1965.
25. Kallman, F. J., Reisner, D. Am. Rev. Tuberc. 1943, 47, 549.
26. Jaco, E. G. (editor) Patients, Physicians and Illness. Glencoe, Illinois,
1958.
27. Mortality Trends in the United States 1954-63. National Center for
Health Statistics series 20, no. 2. Washington, D.C.
28. Puffer, R. Harvard Monographs in Medicine and Public Health no. 5.
Cambridge, Massachusetts, 1944.
29. Lynch, C. C., Pierce-Chase, C., Dubos, R. J. exp. Med. 1965. 121, 1051.
it might be said that idiosyncrasies, modes of recreation and
deportment, physiological adjustments, variations in response
to anxiety and other stresses must influence susceptibility to
infection just as they are known to affect other diseases and
metabolic processes.30-32 Psychosomatic response has been
less well studied in relation to infectious challenge than in
coronary disease, asthma, or peptic ulcer but there is good
evidence 33-37 that personal if not personality factors strongly
influence both communicability and susceptibility in infectious
settings. In the same context, attitude to infectious disease is
an aspect of behaviour which has received attention from a few
investigators 38 39 working mainly in backward communities.
In more complex societies, especially nowadays, attitudes are
perhaps too variable to permit comparable descriptive analysis
but the works of Charles Dickens reveal, in Victorian England,
a fatalistic acceptance of illnesses which were eminently pre-
ventable, just as in the underdeveloped world today the con-
tinuing prevalence of schistosomiasis, sleeping sickness,
malaria, trachoma, and numerous other infections is probably
due at least as much to local attitudes as to any other single
factor. In these various ways, individually and communally,
behaviour can be seen as a prime determinant of infectious
disease.
SOCIAL AND ECONOMIC CONSIDERATIONS
In those countries whichpublish reliable statistics, the
major communicable diseases are always more prevalent
in what are euphemistically described as the under-
privileged or lower socioeconomic groups-i.e., in
ghettos, slums, areas of low employment or of poverty or of
persecution or of warfare. Correspondingly, the few
countries which have evaded or minimised these ways
of living have a uniformly low prevalence of major com-
municable diseases 40 41 though, for reasons stated above,
they have not necessarily overcome the iatrogenic and
other problems connected with infection. If the statistics
are translated into terms of human suffering and in-
efficiency, the importance of crowding, poverty, and
concomitant factors as determinants of the volume and
severity of infection in most countries becomes enormous.
Assessment of this factor is complicated by various inter-
actions (e.g., with the cohort effect of age-group 42 with
nutrition and with ethnic origins) which themselves
embody behavioural and cultural components. One addi-
tional concept which has been examined in Russia 43 is the
matrix of infectious disease created by movements of
human populations. Epidemics have often changed the
course of history but the problems underlying infection
are continuous; epidemics, like wars, occur when the
situation becomes explosive. Because social change is
increasingly dynamic (backwards as well as forwards),
cross-sectional studies are often obsolete before they are
complete and most published reports reflect what has
30. Goldstein, I. Beyond the Germ Theory. Health Education Council,
New York, 1954.
31. Wolff, H. G. Stress and Disease. Springfield, Illinois, 1953.
32. Tanner, J. M. Stress and Psychiatric Disorder. Oxford, 1960.
33. Wolff, C. T., Freidman, S. B., Hofer, M. A., Mason, J. W. Psychosom.
Med. 1964, 26, 576.
34. Feingold, B. F., Gorman, F. J., Singer, J. T., Schlesinger, K. ibid.
1962, 24, 195.
35. Dingle, J., Badger, G. F., Jordon, W. S. Illness in the Home. Cleve-
land, Ohio, 1964.
36. Voors, A. W., Stewart, G. T. Am. Rev. resp. Dis. 1968 (in the press).
37. Brimblecombe, F. S. W., Crinckshank, R., Masters, P. L., Reid, D. D.,
Stewart, G. T. Br. med. J. 1958, ii, 119.
38. Cassel, J. C. in Health, Culture and Community (edited by D. B. Paul).
New York, 1955.
39. Leighton, A. H. My Name is Legion. New York, 1959.
40. Greenwood, M. Epidemics and Crowd Diseases. London, 1935.
41. World Health Organisation Epidemiological and Vital Statistics Reports
20. 1967, vol. xx, 20.
42. Dubos, R., Dubos, J. The White Plague. Boston, Mass. 1952.
43. Pavlovsky, E. N. in Natural Nidality of Transmissible Diseases (edited
by N. D. Levine, translated by F. K. Plous). Urbana, Illinois,
1966.

happened rather than what is happening; as a corollary
to this statement, it should be noted that most so-called
controlled trials of vaccines fail to provide for the con-
tingency that social change per se might have influenced a
given result. Figures published 44 by the U.S. Public
Health Service show clearly that the striking fall in the
reported incidence of poliomyelitis which accompanied
the introduction of the Salk vaccine had in fact begun
earlier. Health problems change when attention is paid
to them: the improvements which followed immunisation
against enteric infections, diphtheria, and tuberculosis
occurred in each case at a time when amelioration in social
and hygienic conditions contributed to a parallel diminu-
tion in these and in other diseases. A similar situation
might even at present be contributing to the success of
newer vaccines. This is not to say that vaccines are in-
effective ; only that, epidemiologically, they have to be
assessed in the light of mobile denominators. Our primary
equation —=P!’dfis lowered by a fall in i as well as
in s, or, more precisely, can be changed into ds/dt=
—P.!!’i which means that ds decreases with P. The same
results can be obtained by a decrease in the number of
infectives i, which occurs sharply when the epidemic has
passed its peak. In community settings, there is there-
fore a mathematical determinant which inevitably
expresses the sum total of all other determinants and
maintains or extinguishes outbreaks of infection. This
thought is by no means new: describing an outbreak of
plague, Thucydides wrote: " Appalling too was the
rapidity with which men caught the infection; dying like
sheep if they attended one another ... no one was ever
attacked a second time, or not with fatal results ... the
crowding of the people out of the country into the city
aggravated the misery, and the newly arrived suffered
most ..." The essential concepts of infectious disease
are encapsulated in this Hellenic vignette.
CONCLUSIONS
My purpose has not been to discount the established
fact that germs can cause disease. Indeed, infection
without a germ would be as impossible, or miraculous, as
conception without a sperm. But, just as pregnancy can-
not be guaranteed by insemination, so disease is not
necessarily produced by access of the germ. It is possible
to assign to different microorganisms different levels of
infectivity more or less in accordance with Theobald
Smith’s equation and with standard dose-response
relationships but only when dependent variables such as
age, sex, genetic homogeneity, inoculum, contact, nutri-
tion, and numerous other factors are rigidly standardised.
This is possible only under experimental conditions and
the outcome is progressively predictable as these condi-
tions, one by one, are rigidly standardised. The vari-
ability of natural infections is proof that these conditions
cannot be met and therefore that the conditions them-
selves are determinants, along with the germ, in causing
infectious disease.
It follows that assessment and control of infectious
disease depends upon recognition, quantitatively where
possible, of these other determinants. It is often easier
to use antibiotics or vaccines than to alter human behaviour
or the environment, but if a disease is maintained because
of attitudes, behaviour, or surroundings, a germ-
orientated approach is unlikely to succeed. Recurrences
of epidemics in hospitals, barracks, schools, and over-
44. U.S. Public Health Service: National Morbidity Report 1935-64.
Communicable Disease Center, Atlanta, Georgia.
1081
crowded or unsanitary communities are proof of this.
Mounting expenditure on antibiotics, vaccines, and
medical care is probably greater than the cost of the
simpler measures required for environmental prophylaxis
The main defect of the germ theory is that it supports an
oversimplified view of the natural basis of infectious
disease. Osler, a firm believer in the theory, described
"
tuberculosis as a social disease with medical aspects ".
It is very unfortunate that striking success in controlling
the medical aspects has not always led to comparable zeal
in controlling the social aspects common to this and most
other communicable disease.
Occasional Survey
THE PRACTICAL MANAGEMENT OF
SEVERE STATUS ASTHMATICUS
N. E. WILLIAMS
M.B. Lpool, F.F.A. R.C.S.
CONSULTANT ANÆSTHETIST, WHISTON HOSPITAL, PRESCOT, LANCASHIRE
JOHN W. CROOKE
M.B., B.Sc. Lond., F.F.A. R.C.S.
ANÆSTHETIC SENIOR REGISTRAR, UNITED LIVERPOOL HOSPITALS AND
LIVERPOOL REGIONAL HOSPITAL BOARD
The emergency treatment of status asth-
Summary
by bronchial lavage and inter-
maticus
mittent positive-pressure ventilation is presented. Though
no technique is perfect, we consider this reliable and
indeed life-saving in those desperately ill patients whose
asthma has become refractory to conventional medical
therapy.
INTRODUCTION
INDICATIONS for the resuscitation of the severe asthmatic
by the use of bronchial lavage and artificial ventilation
have been well documented.l-G They may include
exhaustion and precoma with failure to respond to con-
ventional medical therapy; progressive hypoxia and
hypercarbia; severe cardiac embarrassment with signs of
right ventricular strain; gross tachycardia and pulsus
paradoxus; severe inspiratory wheeze with a silent period
during expiration, suggesting impending closure of the
airway during inspiration, and air-trapping during
expiration.7
The decision to undertake resuscitation is primarily a
clinical one, and urgent action is usually required. It
therefore seems logical to standardise, as far as possible,
the technique adopted, and we describe here the method
we now use in our intensive-care unit.
PROCEDURE
A portable chest X-ray is taken, and an electrocardiographic
record (E.C.G.) is obtained. Continuous monitoring of the
E.C.G. using an oscilloscope, and frequent estimations of the
arterial blood-pressure by sphygmomanometer cuff are
necessary throughout the procedure.
Significant dehydration is invariably a feature of these
critically ill patients, and the resultant hypovolaemia must be
corrected before intermittent positive-pressure ventilation
(i.P.P.v.) is instituted. 1 litre of 5% dextrose is therefore
rapidly infused, followed by 1 litre of saline solution at a slower
1. Broom, B. Lancet, 1960, i, 899.
2. Thompson, H. T., Pryor, W. J. ibid. 1964, ii, 8.
3. Drew, M. J. R., Sando, M. J. W. Med. J. Aust. 1965, ii, 242.
4. Riding, W. D. Practitioner, 1966, 197, 659.
5. Marchand, P., van Hasselt, H. Lancet, 1966, i, 227.
6. Ambiavagar, M., Sherwood Jones, E. Anœsthesia, 1967, 22, 375.
7. Forgacs, P. Lancet, 1967, ii, 203.