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Infection
From Worms to Nucleotides

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N. W. PIRIE, FRS

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Formerly Head of Biochemistry Department, Rothamsted Experimental Station, Harpenden, Hertfordshire, UK

 

Grant-giving bodies often use the word timely, sometimes coupled with the word promise, to describe the
principles used in ailozating money. Research cannot be undertaken on certain themes until technical restraints
have been removed, namely until it becomes possible to attain certain levels of cold, heat, magnification or
pressure. Even a superficial survey of some aspects of the history of biology suggests that, apart from such
physical constraints, timeliness is less a statement about a research project, than about the vision and
receptiveness of the grant-giving body to which the project is submitted. A symposium with the title ‘Of
timeliness and promise - sterile and fruitful approaches in the development of biochemistry’ (December 1978),
gave an opportunity for assembling a few examples, in the general domain of infection, of misjudged timeliness.
This is a slightly expanded version of the paper given at the symposium.

‘I would use (these weapons) and avenge Patroclus,
were it not that flies might settle on his wounds during
my absence, breed maggots, and cause decay.’ That is
Robert Graves’ translation of a conversation at the
beginning of Book 19 of the Iliad. Thetis, who had
given her son, Achilles, the weapons, then reassures
him that she will embaim the corpse with ‘red nectar
and ambrosia’ so that he need not sit by it to keep off
flies, but can take part in the fighting outside Troy.
Homer, or the syndicate that goes by that name, made
a perfectly clear statement that has remained in the
Iliad for nearly 3000 years because it accords with
common experience in farm, kitchen and tomb.

We may wonder therefore what was new in the
experiments published by Redi in 1688.’ He found
that uncovered pieces of meat, from a score of
different animal species, produced maggots of the
same type, but he found none on covered meat. He
claimed no originality; butchers and hunters usually
covered meat at that time to keep off flies. In spite of
the near-universality of classical education, the point
had escaped the attention of scientists and philoso-
phers. They concocted the idea of spontaneous
generation. Having bedevilled biology for a
millennium, it still caused trouble for two centuries
after Redi.

Many points meriting discussion arise from that
story. Why have maggots, or worms to use a general
term common even after Linnaeus, played such an
important role in discussions about the causation of
disease, the preservation of food, and the origins of
life? What is the nature of discovery? Were Homer
and Redi discoverers, because they traced a rational
connection between protection from flies and the
elimination of maggots, whereas butchers and
hunters may merely have been following a ritual or
superstition? People who are not experimentally
minded ‘know’ many things — only a fraction of them

CCC-0308-0188/80/0005-0312$04.00/1
312 INTERDISCIPLINARY SCIENCE REVIEWS, VOL. 5, NO. 4, 1980

true. Separating fact from fiction is as truly discovery
as noticing something that no one had suspected
before.

As Josh Billings remarked ‘It ain’t what a man dont
know that makes a fool of him, it’s what he do know
that ain’t so.’ Finally, why do perfectly definite
observations, and not just suggestions and inter-
pretations that are later found to have merit, so often
lie neglected for decades or centuries? The many
examples that crop up in the history of our knowledge
of various aspects of even a single subject, such as
infection, make it legitimate to wonder whether the
concept of ‘timeliness and promise’, enshrined in
many statements from Research Councils, is not
bogus. Within broad limits, any project which is
within the compass of the physical equipment of the
time, is timely if there is an enthusiast eager to pursue
it.

 

WORMS

 

Until about the beginning of the 19th century,
movement was the usual criterion separating living
from non-living structures. This attitude is shown by
the word viviparous, the phrase ‘the quick and the
dead’ and Coleridge’s comment that scientists ‘could
not hear the life of metals asserted with a more
contemptuous surprise than they themselves incur
from the vulgar, when they speak of Life in mould or
mucor’.” Worms are indubitably alive because they
wriggle; and they are obviously connected with
mortality.

In the confused history of the development of ideas
about infection — the colonization of an organism by
something that multiplies within it - worms have an
important place. Fracastor® seems to have been the

© Heyden & Son Ltd, 1980
first to emphasize the significance of multiplication as
a means of distinguishing infection from poisoning.
Aulus Cornelius Celsus, Rome’s greatest medical
writer (about 50 AD) may have had a glimmer of this
idea; when writing of rabies he used the word virus,
but for snake poison he used venenum. Fracastor
introduced the word fomes for the material that he
suggested was the transmitter of disease from person
to person; he recognized that each infection had a
specific agent and that this multiplied in the host, but
he did not explicitly say that the agent was alive. That
generalization had to wait for the 17th century. Then,
magnifying lenses, and the urge to use them, became
timely.

Reliance on unaided vision is now amazing to us,
when so many even before old age makes it hard to
read small print, have a lens among our pocket
paraphernalia and use it when anything interesting is
noticed. Shakespeare probably did not use a lens.
One version of his comment on the scabies mite runs:

. alittle worme,
Pickt from the lasie finger of a maide,
(Romeo and Juliet, Act I, sc. iv).

But Redi used one to study mite anatomy in detail.
Extensive use was advocated by Glanville,* who
wrote in his Plus ultra (1668) ‘There is an inex-
haustible variety of Treasure which Providence hath
lodged in Things, that to the World’s end will afford
fresh Discoveries’ and went on to mention the ‘...
little Threds and Springs ...’ in an organism
specifically.

 

EARLY MICROSCOPISTS

 

Athanasius Kircher? was already an enthusiastic
microscopist. He saw worms everywhere and was
largely responsible for what Singer called the ‘vermi-
cular obsession’ of the 17th century. Some went so far
as to attribute all disease, indeed even ‘natural’ death
in man and animals, to worms. Bearing in mind how
much of early medicine was developed in warm
countries where maggots develop quickly, this was
not wholly unreasonable. Nevertheless, Avicenna
thought that worms could be beneficial — an interest-
ing forerunner of the occasional use during the
present century of fly maggots for removing dead
tissue from a wound.

Whether or not worms were responsible for dis-
ease, Redi had shown that maggots were not spon-
taneously generated; others doubted the spon-
taneous generation of worms elsewhere. Thus Boyle,
in The sceptical chymist (1661), makes Carneades say
‘...common water ... will putrifie and stink, and
then perhaps too produce moss and little worms, or
other insects, according to the nature of the seeds that
were lurking in it’. Nevertheless, the idea remained
untimely for a further 200 years. Because of a rich
accretion of philosophical, political and theological
associations, it was discussed with a level of acrimony
unusual in scientific debate. Tapeworms domi: -.red
an entertaining phase of the wrangle. Ecclesiastical
dogma seems to have been clear. No new species were
created after the Sixth Day; the spontaneous genera-
tion of anything as elaborate as a tapeworm was
therefore contrary to Holy Writ; Adam and Eve were
perfect before the Fall and therefore could not have
had worms or even a tendency to develop them for
later transmission. The problem seemed insoluble
until the essential intermediate hosts of these
parasites were discovered in the 1840s. Interest in the
place of worms as the cause or consequence of disease
spread into literary circles; Addison, Defoe and Swift
comment on worms seriously or humorously.°

At about the time when belief in worms and insects
generally as causes of disease was beginning to wane,
the idea started that they could be vectors. Malaria
was associated with insects by Lancisi,’ and diseases
that were probably bartonellosis and leishmaniasis
were associated with sand flies by Bueno.® These
associations were more specific than the vague
condemnation of insects by such Roman writers as
Varro and Columella - the latter listed biting insects,
along with visitors, among the hazards of living beside
the main road! These 18th century correlations were
about as good as those that started Reed and Ross on
the control of yellow fever and malaria. The long
interval is interesting. Perhaps it was needed for
insects to recover timeliness after the demise of the
‘vermicular obsession’, perhaps delay was caused by
the intellectual difficulty of separating the roles of
vector and infective agent.

 

GERMS

 

As improvements in microscopy enabled more of the
internal structure of the supposedly simple organisms

 

unskilled people.

 

N. W. PIRIE, FRS, worked in Sir F. G. Hopkins’ laboratory in Cambridge, UK, for 11 years on the
isolation, metabolism and behaviour of glutathione, methionine and other S compounds; on
the antigens of Brucella; and on the isolation of plant viruses. He moved to Rothamsted in
1940 primarily to facilitate virus research, but the move enabled work on the extraction of
edible protein from leaves to be conducted on a larger scale than was possible in Cambridge.
From 1947 to 1973 he was head of the Biochemistry Department at Rothamsted. On
retirement, work on plant viruses ended. Work on leaf protein continues — especially on the
design of simple and robust equipment that could be used for making it by relatively

Address: 42 Leyton Road, Harpenden, Hertfordshire, UK.

 

© Heyden & Son Ltd, 1980

INTERDISCIPLINARY SCIENCE REVIEWS, VOL. 5, NO. 4, 1980 313
to be seen, it became increasingly improbable that
such elaborate structures could simply assemble
themselves. By the beginning of the 18th century,
most biologists had come to agree with Homer and
Redi. But fermentation remained a problem.
Leeuwenhoek asserted that the ‘beasties’ he studied
arose from other organisms only; he saw yeast cells,
but did not assign them a role in fermentation. Boer-
haave” ‘discovered’ that fermentation started more
quickly if material from an old brew was added to the
wort — brewers had, of course, known this for
millennia. Yeast cells were not admitted to the cate-
gory of living organisms until Cagniard-Latour’®
described their reproduction by budding. Chemists,
like Liebig and Wohler, rejected the idea with
contumely and ridicule, but it led to the well-known
series of experiments, notably by Pasteur, on the
precautions needed to keep fermentable fluids from
fermenting. The fact that air carried the particles
needed for the initiation of fermentations and putre-
factions, started Pasteur on the search for identifiable
agents, rather than vague concepts such as contagion
and miasma, as causes of disease. In this he was
following Bassi who, 30 years earlier,'? had trans-
mitted muscardine to silk worms with a needle, and
elaborated from his experiments a reasonably
coherent germ theory of disease.

To a large extent many of us still depend on the
sewage systems and clean water supplies installed in
the middle of the 19th century. Tentative moves
toward slum clearance were also made then. Those
responsible for these improvements, Simon, Snow,”
Nightingale, Virchow and others attached little
importance to micro-organisms though they were
aware of their existence. There is a tendency now to
attach too much importance to the purely micro-
biological consequences of the reforms. The refor-
mers had a more Hippocratic approach and were
concerned with the general phenomena of dirt, air,
food and the standard of living. As Feuerbach -
usually remembered only because Karl Marx
attacked him - put it ‘Do you want to improve
people? Then, instead of preaching against sin, give
them better food’.

As so often in the history of science, trouble was
caused by false antitheses and the difficulty of dis-
tinguishing a necessary, from a necessary and
sufficient, condition. Instead of seeing that personal
constitution, the nature of the environment and the
presence of an infective agent all played a part in the
final appearance of an infectious disease, many
people argued and still argue, for one factor to the
exclusion of the others. As recently as 1847, Sem-
melweiss was ostracized for telling doctors to wash
more often, and washing was counted as one more bit
of heterodoxy in Paracelsus’ (1493-1541) turbulent
career; it has now become timely.

When Lister and Tyndall'* published articles in the
British Medical Journal on the suppuration of wounds
and the role of airborne germs in human disease, they
felt it wise to point out that there was no conflict

314 = INTERDISCIPLINARY SCIENCE REVIEWS, VOL. 5, NO. 4, 1980

between their preoccupation with the immediate
environment of the patient, and the sanitary refor-
mer’s interest in the environment as a whole. They
stressed, as Fracastor had done, the importance of
multiplication. Lister tried to avoid conflict by saying
that it did not really matter whether the ‘septic par-
ticles’ were organisms. However, he thought they
were (see Figs. 1 and 2). In the course of a long
account of operations done aseptically, he said ‘That
they are self-propagating, like living beings, and their
energy is extinguished by precisely the same agencies
as extinguish vitality... is certain, and is of the utmost
practical importance’.

Tyndall was more doctrinaire and wrote ‘Now it is
in the highest degree important to know whether the
parasites in question are spontaneously developed, or
are wafted from without to those afflicted with the
disease. The means of prevention, if not of cure,
would be widely different in (the) two cases’. The
medical profession remained, for a time, unim-
pressed. At an International Sanitary Conference in
1885, Koch’s recent discovery of the cholera vibrio
was not mentioned. However, in spite of the scep-
ticism of Pettenkofer and Metchnikoff, who osten-
tatiously drank cultures supposedly containing the
vibrio, the infectivity of cholera was accepted in 1892.

There are few better examples of compartmen-
talized thinking than the almost complete absence
from all this discussion of any mention of what was
going on in the kitchen. Sausages were preserved with
spices less exotic than Thetis’ ‘red nectar and
ambrosia’, but sausages needed only temporary
preservation! The use of thin pastry casings is more
relevant to the general theme of infection. Every
cook knew that an unopened pie or Cornish pasty
could be kept for longer than an open stew. Cooks did
not, obviously, realize that this was because the dry
casing excluded micro-organisms from the moist
contents; it is odd that scientists did not think about
the matter.

In 1732, C. Carter published ‘The Compleat City
and Country Cook’ (see Fig. 3). This memorably
alliterative work describes in some detail what is in
essence the modern method of bottling fruit. An
anonymous book of receipts had described the bottl-
ing of gooseberries in 1680. As a result, ‘Gooseberry
bottles’ were made until late in the 18th century in
Europe when restrictions on certain raw materials
made it impossible to produce in Britain glass of
suitable quality. At the end of the 18th century the
experiments of Spallanzani provided an explanation
for the efficacy of these techniques. In 1808,
Saddington received a five guinea prize from the
Society of Arts for exhibiting twelve fruits preserved
for two to three years in wide-mouthed wine bottles.
In the light of all that, it is hard to see what was so
novel about Appert’s book", which is usually cited as
having started the food preservation industry. It is
even harder to see why the demise of spontaneous
generation did not become timely until after the later
work of Schwann, Pasteur and Tyndall. It can be

© Heyden & Son Ltd, 1980
 

Figure 1. The Lister carbolic acid spray in use. From W. Watson Cheyne, Antiseptic Surgery,
London (1882). Courtesy of the Wellcome Trustees.

argued that Pasteur and the others did little more
than teach scientists what housewives already knew.

 

VIRUSES

 

Pasteur, like his contemporaries, used the word virus
loosely; when in 1889 his microscope revealed
nothing in a fiuid transmitting rabies, he postulated an
organism similar to those he was familiar with — but
smaller. Filters that were supposed to retain bacteria
were already used at that time so Loeffler and
Frosch,'> who were trying to make a vaccine to
protect cattle against foot and mouth disease, were
surprised by the infectivity of a filtrate. By simple
arithmetic they demonstrated that they were dealing
with an agent that multiplied, and not with a toxin. In
the same year, Beijerinck came to the same
conclusion about tobacco mosaic virus. Although he
was a lifelong friend of the physical chemist van’t
Hoff, he confused matters by calling the agent ‘fluid’
and thus set pathologists off on a metaphysical wild
goose chase about ‘soluble substances’ and ‘particles’
from which some have not yet returned. By accident
these agents, and others found soon afterwards, were

© Heyden & Son Ltd, 1980

called ultramicroscopic or filterable viruses rather
than bacteria: the designation, without the prefix, has
stuck.

Although these viruses multiplied in susceptible
hosts, they did not multiply in cell-free culture media.
Beijerinck stressed this correlation, as did Land-
steiner'® who dismissed, on the grounds that the
medium contained nucleated erythrocytes, the
supposed cell-free cultivation of fowl plague virus.
The generalization that viruses, because of their
absolute dependence on a host, cannot usefully be
classed as organisms, did not become timely for a
further 40 years. The implications of the generaliza-
tion have not yet been fully appreciated: viruses are
still sometimes introduced into discussions on the
origins of life. The dependence of viruses on a host
was an untimely idea; equally untimely observations
were being made at that time. Copeman and
Centanni cultivated viruses in embryonated eggs, and
Landsteiner agglutinated erythrocytes with fowl
plague, a form of influenza, virus. Both tech-
niques were commercialized a generation later (see
Fig. 4).

Bacteria, like plants and animals, vary in composi-
tion according to their age and state of nutrition. It is
reasonable to expect that the scope for variability will

INTERDISCIPLINARY SCIENCE REVIEWS, VOL. 5, NO. 4, 1980 315
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Figure 2. Tyndall’s box in which he studied
the relationship between contamination of the
bacterial culture medium in the glass tubes
and the presences of particles in the air. The
box contained a glass front window (C) as well
as two smaller windows (W) through which a
strong light could be projected thus making
the particles visible. {l) is the lens mount, (a)
and (b) glass tubes to prevent entrance into
the box of unwanted particles and (p) funnel to
fill the tubes. Reproduced from Essays on the
Floating Matter of Air London (1883) courtesy
of Ann Ronan Picture Library; this illustration
was first published by Tyndall in Philos. Trans.
R. Soc. London 27, 166 Part 1 (1876).

be smaller, the smaller the infective agent. When it is
an obligate parasite, in a sense a metabolic product of
the host, it is still more likely to have constant
composition. These expectations, coupled with the
tendency of viruses to be more resistant to chemical
insuit than bacteria, made it reasonable to try to
purify viruses in the chemical sense. Fowl plague virus
was called a globulin by Mrowka,’’ and fowl Pox virus
a nucleoprotein by Sanfelice.'* The evidence that
Schlesinger’’ published for the nucleoprotein nature
of a bacteriophage was much more convincing and
prompted Bawden and Pirie”° to make the cautious
comment on Potato virus X ‘. . . protein is an essential
part of virus ‘X’, but there is no evidence that other
equally important substances may not also be
present’.

Tobacco mosaic virus was called a globulin by
Stanley;' we found”? that it was a nucleoprotein and
went on to show that a dozen other plant viruses, or

316 INTERDISCIPLINARY SCIENCE REVIEWS, VOL. 5, NO. 4, 1980

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Figure 3. Title page of Carter’s famous book
The Compleat City and Country Cook, London
(1732). Courtesy of The British Library.

virus strains, were also nucleoproteins. The presence
of nucleic acid was first disputed; it was then neglec-
ted because of the widespread illusion that nucleic
acids were tetranucleotides and so too small to carry
much specificity. Our suggestion”’ that the nucleic
acid was just as likely as the protein to be important,
was interpreted as our nucleic acid obsession in spite
of the evidence, marshalled by Avery and _ his
colleagues”* that the pneumococcal transforming
factor was nucleic acid. Nucleic acids began to be
considered timely when Hershey and Chase”* found
that more nucleic acid than protein went into a
bacterium when it was infected by a bacteriophage.
The job was completed when Fraenkel-Conrat and
Schramm infected plants with the nucleic acid
separated from tobacco mosaic virus. The inoculum
had to be stronger than usual, but this relegated
protein in viruses to a protective rather than a pri-
mary function and gave nucleic acids their present
dominant role in biochemistry.

 

SOME REASONS FOR DELAY

 

Throughout this account of the growth of knowledge
about processes of infection, I have commented on

© Heyden & Son Ltd, 1980
 

Figure 4. The cultivation of viruses in embryonated eggs. The eggs are inoculated with 0.2 ml of
diluted virus suspension into the allantoic cavity, an automatic syringe being used (Left). After 2-3
days incubation, the eggs are transferred to a cold room to chill the embryos. After a suitable
period of time, the eggs are swabbed with a meth/iodine solution and a circular cut is made in the
shell over the air sac with a trephaning machine (Right). Courtesy of Duncan Flockhart and
Company, London E2.

the fact that several lines of research would have been
timely decades or centuries before they were
pursued. This review may therefore end with some
comments on the general topic of delay. Acceptance
of ideas and observations may, understandably, be
delayed until developments in related sciences have
supplied a congenial intellectual environment. To a
casual observer it seems that Mendel’s observations
on inheritance had to await the rise of biometry,
Waterston’s approach to the gas laws had to await
unequivocal evidence for atomicity, and Wegener’s
suggestions about geodynamics had to await better
bathymetric and magnetic surveys. The list could
easily be extended.

Popular histories of science contain so many stories
of vigorous opposition to ideas which later gained
general acceptance, that it is tempting to think that
sound novel ideas are sure to be opposed. The
thought is sometimes inverted: opposition or neglect
has been regarded as evidence for the soundness of an
idea. But most novel ideas are wrong. The situation is
different with an observation. It may be misinter-
preted, but it cannot be wholly wrong. Thus, to take
an example connected with the theme of infection, in
some communities a priest blesses a new building in
which cheese will be made. Part of the ritual involves
rubbing it with old cheese. Presumably the ritual
works: which is the effective part of it is a matter of
opinion and for later experiment. When a technique
is observed to work, it is hard to understand why the
attempt to find out the reason is so often delayed.

© Heyden & Son Ltd, 1980

Louis Racine (fils) remarked ‘. . . in order better to
humiliate those who cultivate the sciences, God has
permitted the finest discoveries to be made by chance,
and by those least apt to make them. The sea compass
was not invented by a mariner, nor the microscope by
a physicist, nor printing by a writer, nor gunpowder
by a soldier’.?° We can add that Priestley was a
non-conformist minister, Boussingault a mining
engineer, Pasteur a crystallographer, and the first
observations on current electricity were made by
biologists. This sort of thing annoys specialists. They
think, naturally, that advances in their subject should
be made by them. The argument goes back a long way
in both time and epistemology. Posidonius, who was a
philosopher, said that innovations were made by
philosophers: Seneca (90th Epistle) said they were
made by workmen. In The fable of the Bees, Bernard
de Mandeville discussed the issue and agreed with
Seneca, so did Adam Smith in The Wealth of Nations.

When outsiders make suggestions or observations,
opposition or neglect are understandable. Disregard
for observations made by people with orthodox
qualifications, and on subjects later given great
importance, is harder to understand. The ‘Non-
conservation of Parity’ is an excellent example with
biological implications. The Nobel Prize for physics
was awarded to Lee and Yang within a year of their
observation of chirality in some atomic processes.
Research on the subject was then undertaken with
such enthusiasm, or mania, that another physicist had
to withdraw five papers because his dream world had

INTERDISCIPLINARY SCIENCE REVIEWS, VOL. 5, NO. 4, 1980 317
intruded on his experiments! Franklin,”’ in a
thoughtful discussion of the whole matter, points out
that similar observations had been reported, and
neglected, 29 years earlier.

Fortuitously, newspaper accounts of Lee and
Yang’s observation coincided with a New York
Academy of Sciences symposium on ‘Modern ideas
on spontaneous generation’ held at the end of 1956.
Pasteur regarded the preferential use of only one of
the isomers of a chiral molecule as a peculiarly bio-
logical phenomenon. During the 1930s it became
clear that, although individual members of a group of
molecules such as the amino acids rotated the plane of
polarization of light in either direction, all members
of the group had the same configuration in 3-dimen-
sional space. The origin and significance of chiral
preference was therefore regularly discussed in
papers on biopoesis. The possibility that it was the
consequence of some fundamental atomic asymmetry
was therefore an important subject of conversation
of those attending the symposium. The sudden
excitement about parity in physics laboratories can
hardly be explained by this biological interest because
that did not emerge in print until 1960.”° All that
Franklin feels able to conclude is that‘... not only the
physical and logical content of an experiment deter-
mines whether it is crucial or not.’

From one point of view, the present-day influence
of think-tanks and the increasing control of research
by civil servants could be beneficial. It is often easier

to get a non-specialist than a specialist to understand
the essence of a new idea, or the significance of an old
observation — fewer layers of habit and conventional
wisdom have to be peeled away. On the other hand,
the non-specialist usually submits the matter to a
specialist committee and, unless very obstinate,
accepts condemnation by the committee. The basic
fallacy underlying the British customer/contractor
principle of financing research is the assumption that
the customers know enough about what it might be
possible for them to get, to know what to ask for. That
is the sort of knowledge that people who actually
handle material and equipment are most likely to
have. The point was well put by Mees, who directed
research for Eastman Kodak.

‘The best person to decide what research shall
be done is the man who is doing the research. The
next best is the head of a department. After that
you leave the field of best persons and meet
increasingly worse groups. The first of these is the
research director, who is probably wrong more
than half the time. Then comes a committee
which is wrong most of the time. Finally there is
a committee of company vice-presidents,
which is wrong all the time.’?”

That may be an extreme point of view. Neverthe-
less, it recognizes the fact that developments are most
likely to come from people with practical experience,
especially if that experience extends to what is
happening in factory, farm and kitchen.

NOTES AND LITERATURE CITED

 

1. F. Redi, Esperienze intorno alla generazione deg!' insetti
(1668).

2. S. T. Coleridge, Hints towards the formation of a more
comprehensive theory of life, ed. by S. B. Watson (1848).

3. H. Fracastor, De sympathia et antipathia rerum, fiber
unus. De contagione et contagiosis morbis et curatione
(1546).

4. J. Glanville, Plus ultra: or the advancement of knowledge
since the days of Aristotle. In an account of some of the
most remarkable late improvements of practical, useful
learning: to encourage philosophical endeavours.
Occasioned by a conference with one of the notional way
(1668).

5. A. Kircher, Serutinium physico-medicum contagionsae
etc. (1658).

6. For example: D. Defoe in A journal of the Plague Year
(1722), J. Addison in various articles in The Tatler and The
Spectator about 1710, and J. Swift, in Remarks upon a
book, intitled, the Rights of the Christian Church asserted,
against the Romish, and all other Priests, who claim an
Independent Power over it (1708). Swift wrote of a man
who believed that ‘... all we eat and drink, all the whole
consistence of human bodies, and those of every other
animal, the very air we breathe; in short, all Nature
throughout was nothing but worms: and by that system,
he solved all difficulties, and from thence all cases in
philosophy’.

7. G. M. Lancisi, De noxiis paludum effluviis eorumque
remediis (1718).

8. A. Herrer and H. A. Christensen, Implication of Phie-
botomus sand flies as vectors of Bartonellosis and
Leishmaniasis as early as 1764. Science 190, 154 (1975).

9. H. Boerhaave, Elementa chemiae (1732).

10. C. Cagniard-Latour, Mémoire sur la fermentation vineuse.
C. R. Acad. Sci. 4, 905 (1837).

318 INTERDISCIPLINARY SCIENCE REVIEWS, VOL. 5, NO. 4, 1980

11. A Bassi, Def mal del segno calcinaccio o moscardino,
malattia che affligge i bachi da seta e sul modo di liberarne
le bigattaje anche le piu infestate (1835).

12. Dr John Snow is best known for the part he played in
stopping the cholera outbreak in Broad Street, London, in
1854. A pub on the corner of Broadwick and Lexington
Streets in London’s West end was renamed ‘The John
Snow’ to celebrate the centenary of that outbreak. It is
clear from the historical material displayed in that pub
that the local residents disliked the squalor and stench
intensely. For example, they wrote to the editor of The
Times ‘Sur, — May we beg and beseach your proteckshion
and power, We are Sur, as it may be, living in a Wilder-
ness, so far as the rest of London knows anything of us, or
as the rich and great people care about. We live in muck
and filth. We aint got no Priviy, no dust bins, no drains no
water-splies and no drain or suer in the hole place...’.

13. J. Lister, Address in surgery. Brit. Med. J. 227 (26/8/1871);
J. Tyndall, Dust and disease. Brit. Med. J. 661 (24/6/1871).

14. N. F. C. Appert, L’art de conserver pendant plusieurs
anneés toutes les substances animales et végétales
(1810).

15. F. Loeffler and P. Frosch, Berichte der Kommission zur
Erforschung der Maul—und Klauenseuche bei dem Insti-
tut fdr Infektionskrankheiten in Berlin. Zentra/b/. Bakteriol.
Parasitenkd. 23, 371 (1898).

16. K. Landsteiner and M. Berliner, Ueber die Kultivierung des
Virus der Hthnerpest. Zentralb/. Bakteriol. Parasitenkd.
67, 165 (1912).

17. Mrowka, Das Virus der HUhnerpest ein Globulin.
Zentralbl, Bakteriol. Parasitenkd. Abt. 1 Orig. 67, 249
(1912).

18. F. Sanfelice, Untersuchungen Uber das Epithelioma
contagiosum der Tauben. Z. Hyg. Infektionskr. 76, 258
(1914).

© Heyden & Son Ltd, 1980
19

20.

21,

22.

23.

24.

. M. Schlesinger, The Feulgen reaction of the bacterio-
phage substance. Nature (London) 138, 508 (1936) and
earlier papers.

F. C. Bawden and N. W. Pirie, Experiments on the chem-
ical behaviour of potato virus ‘x’. Br. J. Exp. Pathol. 17, 64
(1936).

W. M. Stanley, Chemical studies on the virus of tobacco
mosaic. VI. The isolation from diseased Turkish tobacco
plants of a crystalline protein possessing the properties of
tobacco mosaic virus, Phytopathology 26, 305 (1936).
F.C. Bawden, N. W. Pirie, J. D. Bernal and |. Fankuchen,
Liquid crystalline substances from virus-infected plants,
Nature (London) 138, 1051 (1936).

F. C. Bawden and N. W. Pirie, Virus multiplication consi-
dered as a form of protein synthesis in The Nature of virus
multiplication ed. by P. Fildes and W. E. van Heyningen.
Cambridge University Press, Cambridge (1953).

O. T. Avery, C. M. McLeod and M. McCarty, Studies on the
chemical nature of the substance inducing trans-

25.
26.
27.
28.

29,

formation of pneumococcal types. Induction of trans-
formation by a desoxyribonucleic acid fraction isolated
from pneumococcus type Ill. J. Exp. Med. 79, 137 (1944).
A. D. Hershey and M. Chase, Independent functions of
viral protein and nucleic acid in growth of bacteriophage.
J. Gen. Physiol. 36, 39 (1952).

Quoted from Nat. Resour. 10(3), 2 (1974).

A. Franklin, The discovery and non-discovery of parity
non-conservation. Stud. Hist. Philos. Sci. 10, 201 (1979).
J.B. S. Haldane, Pasteur and cosmic asymmetry. Nature
(London) 187, 879 (1960).

Quoted from Biograph. Mem. Fellows R. Soc. 7, 182
(1961).

The manuscript was received 6 June 1980
© Heyden and Son Ltd, 1980

 

 

Fumigation of the special artist of the /lustrated
London News when covering the Hamburg cholera
epidemic in 1892. From /ilustrated London News, 17

September 1892.

Library.)

© Heyden & Son Ltd, 1980

(Courtesy Ann Ronan Picture

INTERDISCIPLINARY SCIENCE REVIEWS, VOL. 5, NO. 4, 1980 319