WEBVTT

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Prof: Well good morning.

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I think we should get started.

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And what we'll be talking about
this morning is the germ theory

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of disease.

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In a sense, it's taken us half
a course to reach a period when

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we begin to see the development
of what you would probably

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recognize as a scientific modern
medicine.

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To appreciate the enormity of
what happened with the germ

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theory of disease,
I think it's worth casting our

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eye back to a point we had
already reached.

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Let's say we compared the year
1789 with 1900.

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Before 1789,
and the developments with the

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Paris School of Medicine,
you'll remember the conceptual

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framework was dominated,
still, by that of Hippocrates,

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Galen and humoral medicine.

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Humoralism was in retreat,
as doctors were absorbing ideas

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about the circulatory system,
and the nervous system.

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But the medical philosophy,
the vocabulary,

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therapeutics and medical
education,

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were still cast in the old
framework,

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supplemented by other
developments--

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astrology, for example--and
epidemic diseases were thought

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to be explained by the doctrine
of miasma--

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that is, the corruption or
poisoning of the air--

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or malaria, as it was called at
the time.

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By 1900, I think it's clear
that more change had occurred

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than in all of the centuries
since Hippocrates combined,

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and that medical science,
whose basic principles were

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recognizably similar to our own
today,

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had emerged.

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Furthermore,
the speed of change was

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gathering momentum as the
nineteenth century progressed.

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The closing decades of the
century witnessed a wholesale

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revolution, with the germ theory
of disease as its central

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feature.

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This theory,
I'm going to argue,

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was as important a revolution
in medicine as for,

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example, Galileo's theory of
the rotation of the earth was to

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astronomy;
or perhaps Darwin's theory of

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natural selection was to
biology;

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or gravitation to physics.

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So, what I would like to begin
with then is looking at what is

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the germ theory?

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What were its preconditions?

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Who were the decisive figures?

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What were the decisive events
associated with that famous trio

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of Louis Pasteur,
Joseph Lister,

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Robert Koch?

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What were the implications?

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Let's avoid the idea of a
single genius coming up with a

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great idea.

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Let's question the vision
behind the idea of the Nobel

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Prize.

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I'm going to be arguing that
these discoveries,

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that culminate in the germ
theory, had a long gestation

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period,
and were a collective process

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that required a long train of
preconditions.

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Let's look at the preconditions
first.

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I'll argue that they're
conceptual, technological and

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institutional.

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Let's look at conceptual
preconditions.

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The germ theory of disease
didn't arise directly out of

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hospital medicine and the Paris
School,

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but I think it's inconceivable
without the background of that

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development.

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It was crucial to have a
nosology--that is,

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disease classification--the
idea of disease specificity--

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that they were specific
entities--and without the idea

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of localism;
that is, lesions.

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And also essential was the new
development of pathological

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anatomy, derived from the
post-mortem in the Paris

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hospitals.

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The idea of specificity was
critical.

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Any further progress to the
idea of a microbial disease

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depended on the view that
diseases didn't transform from

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one into another.

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Before the Paris School,
it was common to believe,

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for example,
that cholera--to take one

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disease--
was simply a heightened form of

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endemic summer diarrhea.

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It wasn't a specific disease,
and it grew out of another

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preexisting condition.

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The germ theory depended
instead on the conviction that

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there are stable,
unchanging disease entities,

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that each one is specific and
has a specific microbial cause.

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But the followers of
Louis--Pierre Louis,

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that is--in Paris,
while carefully distinguishing

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one disease from another,
and classifying them,

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didn't advance much towards the
idea of the causative pathogens

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behind them.

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Now, when we've talked about
the Paris School,

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I don't want to give you the
idea that all of the crucial

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figures in disease specificity,
and nosology, were French.

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There were other crucial
figures as well.

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William Gerhard,
who distinguished typhus from

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typhoid.

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He had studied in Paris with
Louis for a couple of years,

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and then returned to his native
Philadelphia.

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During an epidemic of typhus,
he dissected hundreds of

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cadavers and discovered that
their lesions had no resemblance

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whatsoever to typhoid.

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There was William Budd,
who wrote an important book

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called Typhoid Fever:
Its Nature, Mode of Spreading

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and Prevention,
in 1873.

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And he referred to the
unchanging, specific nature of

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the disease.

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Let's listen to what he said.

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He said this:
"To propagate itself and

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no other,
and that on a series of

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indefinite progressions,
constitutes the very essence of

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the relation on which the idea
of species is founded.

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How much this applies in the
animal and plant world we all

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know.

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It is strange that what it
implies, in the case of

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diseases, should be so seldom
recognized until now."

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Or there was Pierre Bretonneau,
who believed that there were

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morbid seeds that caused special
diseases,

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just as every seed--in the
natural history,

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that is--gives rise to a
determined species.

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And he applied that idea to
diphtheria.

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Just so as apples don't turn
into wheat--apples seeds into

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wheat--so too endemic diarrhea
doesn't transform itself into

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Asiatic cholera.

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There was an important
transitional figure too.

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Claude Bernard,
of the Paris School,

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one of its stars,
who lived from 1813 to 1878,

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and in 1865 wrote an important
book called An Introduction

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to the Study of Experimental
Medicine,

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where he presented a critique
of the Paris School.

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He argued that diseases were
dynamic processes.

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They weren't static in the way
that the Paris idea of nosology

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seemed to suggest.

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And he argued that they,
hospitals, displayed the end

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stages of diseases,
not their beginnings.

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And he argued that hospitals
and clinics had an excess of

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variables that wasn't helpful
for the further development of

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medical science.

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So, he proposed an alternative,
that was embodied in his title;

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that is, experimental medicine.

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And by that,
he meant laboratory medicine.

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He's one of the people who
suggest a new epistemology for

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medicine,
which isn't the hospital ward

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but the lab,
where you could have the

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experimental testing of single
variables in controlled

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settings.

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Here was a new source of
medical knowledge.

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If that provides conceptual
preconditions,

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there were also institutional
ones.

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And here I'm thinking of the
rise of the laboratory,

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of the university;
that is, full-time professional

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scientists, research
institutions,

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and Germany leading the way,
rather than France,

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in this development.

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There were also technological
foundations.

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It's impossible to think of the
rise of the germ theory of

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disease without microscopy.

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And so it was indebted to Anton
van Leeuwenhoek,

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who lived from 1632 to 1723,
and developed the simple

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microscope.

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And then in the 1820s,
and thereafter,

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there were major improvements:
the development of the compound

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microscope and higher
magnification,

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the work of the Zeiss Company
and the development of lenses.

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There was also,
for a fourth precondition,

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a lonely, neglected pioneer,
and that was a Hungarian

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gynecologist,
who lived in Vienna,

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called Ignaz Phillip
Semmelweis,

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whose crucial idea,
which dates from the 1840s--

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Semmelweis noted that the
infection rate in childbirth was

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much lower on obstetrical wards
where women were delivered by

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midwives,
rather than on wards where they

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were delivered by physicians.

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The reason had nothing to do
with their training or relative

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degree of benevolence and
malevolence.

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The point was that the
physicians were just returning

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from post-mortem examinations,
from autopsies,

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after which,
at that time,

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they didn't wash their hands,
and so they were transmitting

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disease to their patients,
from autopsies they were

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performing in an adjacent
building.

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So, Semmelweis,
suspecting--although he didn't

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know the mechanism--
that this was the case,

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established elaborate
hand-washing rituals,

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using a chlorinated lime
solution--a little bit the first

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hand sanitizer,
we might say--and he noted that

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mortality plummeted from twenty
percent to one percent.

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Unfortunately,
his own career was not a happy

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one.

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He was mocked by his colleagues
as a charlatan,

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and was actually demoted in his
own hospital.

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Well, then, there's a fifth
precondition,

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and that's the development of
the basic sciences.

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And it's hard to imagine,
as we'll see in a minute,

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the rival of the germ theory
without chemistry in particular.

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The specific issue that gave
rise to the germ theory of

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disease was fermentation.

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And Pasteur,
after all, was originally a

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chemist, who in the 1860s became
a biologist, and we should note

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that he wasn't a physician.

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This is to introduce you to
Louis Pasteur.

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The immediate background to the
germ theory of disease involved

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the dominant theory of the day,
which was called the zymotic

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theory of disease;
that is, that it was a form of

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ferment--a little bit like
Pettenkofer had asserted--caused

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by some fermentation of decaying
organic material.

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Under the right conditions of
soil, temperature and moisture,

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this fermentation would give
off a poison into the

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environment.

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Also quite widespread was the
idea of spontaneous generation,

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that diseases arose somehow
spontaneously in a particular

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locality,
weren't brought in or imported

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from the outside.

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There was a famous experiment
about this, from the seventeenth

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century.

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It was Redi's maggot experiment.

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The idea was that if you could
have rotting meat,

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and you could cover it,
you wouldn't develop maggots.

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But if you didn't cover it,
then you would find that it was

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full of maggots.

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So, the maggots didn't appear
in the rotting meat by some

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internal mechanism of
spontaneous generation,

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but were imported from outside.

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And Pasteur,
as we'll see in a minute,

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takes up this very idea,
to the idea that germs too,

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like the maggots,
are imported from outside.

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The immediate issue for Pasteur
was in fact fermentation.

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He began by studying the
fermentation of wine and beer,

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and in particular their
spoilage.

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At the time,
this was thought,

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when he took up his work,
to be a chemical process.

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And remember that Pasteur was
not a physician but a chemist

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originally.

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Well, what he did was to
discover that the fermentation

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was caused instead by living
microorganisms,

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bacteria that he identified
through the microscope.

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Now, this was a high-profile
investigation in the 1860s,

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for the simple reason that the
production of wine and beer

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involved two of France's major
economic activities.

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Pasteur--and this was part of
his genius--immediately made a

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far-reaching connection.

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In his estimate,
the fermentation that he saw in

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wine and beer,
now caused by bacteria,

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was analogous to putrefaction
and infection in wounds,

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for example.

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So, he began to regard disease
as a process involving

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microorganisms,
living things.

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This was work that Pasteur
conducted in the late 1850s and

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1860s,
and it marked the first

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transformation in his career
from that of a chemist into a

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biologist,
or we might say today a

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microbiologist.

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He examined not only wine and
beer,

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he then turned his attention to
milk and its souring,

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and he wrote a book on that,
and then a study on wine and a

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study on beer.

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Now, of great importance was
the fact that Pasteur's

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discovery that abnormal
fermentation leads to spoilage,

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along with that went another
discovery he made,

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which was that this process
could be controlled by heat.

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Here was a major public health
discovery, and that led to the

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process we now know as
pasteurization.

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So, already in the 1860s,
Pasteur was busily transforming

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biology.

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Even if had he stopped then,
his discoveries were already

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those of a fully productive
life's work.

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But then in the 1860s came a
turn in Pasteur's interests from

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biology, more specifically to
medicine and public health.

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And he began to study
spontaneous generation.

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Now, followers of Pasteur
believed instead in biogenesis.

17:40.480 --> 17:44.770
With regard to cholera,
that we already examined,

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about which there was a debate,
the idea was that cholera was

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imported from outside.

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It didn't arise spontaneously.

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It wasn't the transformation of
some other disease that already

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existed into cholera.

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Rather it was a specific
disease that could not arise as

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a heightened form of a
pre-existing condition.

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Pasteur also devised--well,
Koch didn't think this was so

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elegant,
but it certainly convinced

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Pasteur and his followers--
a famous swan neck flask

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experiment.

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That is, he sterilized a flask
with a swan's neck,

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and found that if the culture
is boiled,

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and the flask prevents air from
gaining access to it,

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then there was no development
inside of organisms that we

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would call bacteria.

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A culture of them could grow in
the flask, only if germs were

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allowed to enter it.

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But if the neck of the flask is
broken and air is emitted--you

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can see the neck broken at the
bottom--then you get a luxurious

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development of life.

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And this had enormous
implications for diseases and

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wounds.

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Pasteur wrote simply,
"There is no known

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circumstance in which it can be
confirmed that microscopic

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beings came into the world
without germs,

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without parents similar to
themselves."

19:28.598 --> 19:33.408
Now, Pasteur's success was
partly based on the fact that he

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was aware of the full range of
the scientific implications of

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his work,
and he selected carefully

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topics with high profile,
philosophical and biological

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interest.

19:46.930 --> 19:50.750
He was an expert at cultivating
the media.

19:50.750 --> 19:56.410
That was one reason that
spontaneous generation had led

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to so much excitement.

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But most decisive in Pasteur's
work was what he did in the

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1870s,
as he turned to diseases,

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demonstrating the full
implications of his ideas on

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fermentation in the previous
decade.

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This new phase of discovery
occurred,

20:19.170 --> 20:23.900
despite the fact that in 1868
he suffered a major cerebral

20:23.897 --> 20:27.087
hemorrhage,
that left him paralyzed on his

20:27.086 --> 20:27.826
left side.

20:27.828 --> 20:32.198
What did Pasteur do in the
1870s that was so crucial?

20:32.200 --> 20:36.620
Well, first of all,
I'll look at two major things

20:36.619 --> 20:37.909
that he did.

20:37.910 --> 20:42.760
One is work with silkworms,
and the other is work with

20:42.762 --> 20:45.512
chicken cholera and anthrax.

20:45.509 --> 20:49.989
The first thing was a major
contribution to the germ theory

20:49.987 --> 20:54.157
of disease, accomplished by the
work with an unexpected

20:54.156 --> 20:58.406
experimental animal;
that is, the silkworm.

20:58.410 --> 21:03.180
And again let's look at the
fact that Pasteur's success,

21:03.180 --> 21:07.820
his influence and his genius,
was in part the fact that he

21:07.823 --> 21:11.573
took on really high-profile
research topics;

21:11.568 --> 21:14.938
that is to say,
disease of silkworms,

21:14.935 --> 21:19.705
where these diseases were
decimating one of France's

21:19.705 --> 21:23.255
leading industries,
that is, silk.

21:23.259 --> 21:26.909
Through meticulous and
painstaking research,

21:26.911 --> 21:32.181
Pasteur demonstrated that there
were two major diseases at work

21:32.176 --> 21:34.976
affecting France's silkworms.

21:34.980 --> 21:40.170
He called them pebrine and
flacherie--you needn't remember

21:40.172 --> 21:45.452
them for our purposes--and
asserted that both were specific

21:45.454 --> 21:48.374
diseases caused by bacteria.

21:48.368 --> 21:51.878
And he immediately realized
that there were enormous

21:51.880 --> 21:54.360
implications,
not only for silkworms,

21:54.357 --> 21:56.627
but for human beings as well.

21:56.630 --> 22:01.010
He isolated then two germs
affecting silkworms,

22:01.009 --> 22:06.239
and demonstrated that they were
responsible for specific

22:06.244 --> 22:08.534
contagious diseases.

22:08.528 --> 22:13.358
Pasteur isolated a germ and
convincingly linked it with a

22:13.355 --> 22:17.415
specific disease,
and the concept of specificity

22:17.416 --> 22:22.086
was at the basis then of the
whole idea of the germ theory of

22:22.092 --> 22:22.952
disease.

22:22.950 --> 22:27.770
Now you know Pasteur didn't
invent the idea of contagion.

22:27.769 --> 22:30.249
You've seen it with Fracastoro.

22:30.250 --> 22:34.090
You've seen it in John Snow,
who talked about the

22:34.088 --> 22:36.408
possibility of animalcules.

22:36.410 --> 22:39.680
And there were other
scientists--Casimir Devaine in

22:39.675 --> 22:42.105
France,
the English physician John

22:42.107 --> 22:45.147
Sanderson--
who were also advancing a

22:45.146 --> 22:49.756
hypothesis that they were
finding microbes with their

22:49.759 --> 22:53.379
microscopes,
and hypothesizing that they

22:53.381 --> 22:55.991
might be the agents of disease.

22:55.990 --> 23:00.590
But Pasteur was the first to
provide a demonstration in a

23:00.592 --> 23:04.572
specific case,
proving that microbes were the

23:04.568 --> 23:08.008
causative agents of specific
diseases,

23:08.009 --> 23:13.109
and he provided a methodology
for further experimentation and

23:13.108 --> 23:14.128
discovery.

23:14.130 --> 23:18.520
Pasteur then turned from
silkworms to diseases,

23:18.515 --> 23:22.895
the diseases of chicken cholera
and anthrax.

23:22.900 --> 23:27.480
Neither is responsible for
extensive human disease,

23:27.479 --> 23:31.509
as both are causes of diseases
of animals.

23:31.509 --> 23:35.209
But what was critical was the
process.

23:35.210 --> 23:39.140
His work on anthrax helped to
establish a model for

23:39.141 --> 23:42.051
investigating infectious
diseases,

23:42.048 --> 23:46.338
and establishing the claims for
the germ theory of disease,

23:46.338 --> 23:50.428
and putting that on solid
foundation.

23:50.430 --> 23:53.900
At the same time,
he made another major

23:53.901 --> 23:55.181
development.

23:55.180 --> 24:00.200
His vision went beyond simply
demonstrating the germ theory,

24:00.201 --> 24:02.161
although he did that.

24:02.160 --> 24:05.720
In addition,
he developed a public health

24:05.721 --> 24:08.471
practice--
that is, vaccination,

24:08.467 --> 24:12.457
which had been pioneered a
hundred years before--

24:12.460 --> 24:16.860
and he helped now to found the
discipline of experimental

24:16.857 --> 24:17.877
immunology.

24:17.880 --> 24:21.130
Now, let's--we've seen
vaccination and the work of

24:21.128 --> 24:22.188
Edward Jenner.

24:22.190 --> 24:23.190
Let's define.

24:23.190 --> 24:29.030
Vaccination is the introduction
into the body of either the

24:29.032 --> 24:32.832
whole,
or part, of a disease-causing

24:32.827 --> 24:36.837
microorganism,
in order to teach the immune

24:36.837 --> 24:40.117
system to attack that same
organism,

24:40.118 --> 24:45.548
should it reappear in the body
through natural processes.

24:45.548 --> 24:50.308
The mechanism is that the
vaccine primes the immune system

24:50.310 --> 24:54.850
to produce antibodies,
or teaches immune cells to

24:54.848 --> 24:58.238
recognize and attack the
organism,

24:58.240 --> 25:00.880
that we now know perhaps to be
a virus,

25:00.880 --> 25:05.080
a bacterium,
or a parasite of a different

25:05.084 --> 25:05.824
kind.

25:05.818 --> 25:09.858
The problem,
of course, was how to stimulate

25:09.859 --> 25:13.149
immunity without causing
disease.

25:13.150 --> 25:19.320
Jenner benefited from the
cross-over immunity from cowpox

25:19.317 --> 25:20.857
to smallpox.

25:20.859 --> 25:23.369
Pasteur did something else.

25:23.368 --> 25:27.178
He used the concept of
attenuation.

25:27.180 --> 25:30.860
Jenner is the father of
immunology, in a sense,

25:30.858 --> 25:34.778
Pasteur the founder of
experimental immunology.

25:34.779 --> 25:40.369
The idea he had was that live
pathogens could be introduced in

25:40.369 --> 25:43.819
the body,
but only after being treated in

25:43.824 --> 25:46.344
some way--
heat, for example,

25:46.339 --> 25:51.569
or passage through a different
host first was another--

25:51.568 --> 25:56.228
in such a way then that their
virulence is diminished.

25:56.230 --> 25:59.820
Then they'll stimulate the
immune response,

25:59.818 --> 26:04.688
without causing disease at all,
or only a mild disease.

26:04.690 --> 26:09.120
This discovery was made during
his work with the bacterium that

26:09.115 --> 26:11.825
causes chicken cholera,
made sort of by

26:11.826 --> 26:14.536
chance--serendipity played a
role.

26:14.538 --> 26:19.248
He left a batch of bacteria
untouched for a week or so while

26:19.249 --> 26:23.319
he went on vacation during the
hot summer months.

26:23.318 --> 26:26.028
On returning,
he found initially,

26:26.029 --> 26:29.839
to his frustration,
that the culture no longer

26:29.840 --> 26:34.330
produced the disease when he
attempted to infect other

26:34.328 --> 26:35.598
chickens.

26:35.598 --> 26:40.228
So, he got a fresh batch of
bacterium, and injected the same

26:40.226 --> 26:43.356
chickens with it,
as well as a lot of new

26:43.362 --> 26:46.972
chickens, and made a surprising
discovery.

26:46.970 --> 26:51.040
That the original chickens,
injected with the old vaccine,

26:51.038 --> 26:55.428
remained healthy--in our terms,
they were immune--

26:55.430 --> 27:00.070
while the new and previously
untreated chickens sickened and

27:00.068 --> 27:00.618
died.

27:00.618 --> 27:03.908
He repeated the experiment
several times,

27:03.910 --> 27:08.620
with the same results,
and concluded that the summer

27:08.616 --> 27:14.336
heat had changed or attenuated
the culture of the bacterium.

27:14.338 --> 27:18.818
Later techniques expanded the
repertoire, demonstrating that

27:18.820 --> 27:23.300
heat could kill vaccines of
chicken cholera but still induce

27:23.301 --> 27:24.291
immunity.

27:24.288 --> 27:28.948
There were other vaccines that
could employ live but attenuated

27:28.946 --> 27:30.596
bacteria or viruses.

27:30.599 --> 27:33.369
Some used killed microorganisms.

27:33.369 --> 27:36.019
Some used sub-unit vaccines.

27:36.019 --> 27:39.799
And the processes of
attenuation are not only heat,

27:39.798 --> 27:43.678
but let's say for polio,
could be the passage through

27:43.680 --> 27:47.020
formaldehyde and various--
there are other means.

27:47.019 --> 27:51.629
Attenuation though was critical
to the development of vaccine as

27:51.633 --> 27:53.613
a public health strategy.

27:53.609 --> 27:56.149
But let's return to Pasteur.

27:56.150 --> 27:59.780
Having discovered attenuation
with chicken cholera,

27:59.784 --> 28:03.424
Pasteur applied the same
principle to the different

28:03.417 --> 28:05.087
disease of anthrax.

28:05.088 --> 28:09.568
The pathogen responsible was
the Bacillus anthracis

28:09.574 --> 28:13.434
that had recently been isolated
by Robert Koch.

28:13.430 --> 28:17.030
And if you see the film,
The Story of Louis

28:17.034 --> 28:22.244
Pasteur, you'll see what he
did in 1881 with the bacterium.

28:22.240 --> 28:26.810
In a famous experiment,
he vaccinated twenty-four sheep

28:26.807 --> 28:30.787
with an attenuated--
that is, heated--bacterium,

28:30.785 --> 28:35.485
after which he challenged the
original twenty-four sheep with

28:35.487 --> 28:38.697
live unattenuated anthrax
injections,

28:38.700 --> 28:42.970
as well as twenty-four control
sheep that had not been

28:42.971 --> 28:44.021
vaccinated.

28:44.019 --> 28:47.049
The vaccinated sheep remained
healthy.

28:47.049 --> 28:50.479
The non-vaccinated all died.

28:50.480 --> 28:55.160
Then came the 1880s,
and Pasteur turned to another

28:55.161 --> 28:59.271
high profile disease,
and that is rabies.

28:59.269 --> 29:04.059
Having discovered attenuation
by heat, with chicken cholera

29:04.057 --> 29:09.007
and anthrax, Pasteur extended
the principle of attenuation by

29:09.009 --> 29:10.329
other means.

29:10.328 --> 29:14.278
This involved further famous
experiments.

29:14.278 --> 29:17.848
Rabies, as it turns out,
was not another bacterial

29:17.849 --> 29:22.659
disease, but a disease caused by
what we now know to be a virus.

29:22.660 --> 29:25.890
In this case,
he attenuated the virus by

29:25.885 --> 29:30.345
isolating it from foxes,
and then passing it through an

29:30.354 --> 29:33.834
unnatural host of a different
species;

29:33.829 --> 29:36.749
in this case, the rabbit.

29:36.750 --> 29:40.350
So, passing the virus through a
series of rabbit bodies,

29:40.348 --> 29:43.958
he succeeded in producing a
variant that would no longer

29:43.959 --> 29:49.279
cause the infection in foxes,
but would serve to protect

29:49.280 --> 29:53.990
against the natural occurring
rabies.

29:53.990 --> 29:57.890
Rabies was not a high impact
disease,

29:57.890 --> 30:00.950
in terms of numbers of people
it affected,

30:00.950 --> 30:03.080
but it was a disease of high
drama,

30:03.078 --> 30:06.298
and one that was then,
and still is,

30:06.299 --> 30:08.909
universally fatal.

30:08.910 --> 30:12.490
So, it was ideal for attracting
media attention.

30:12.490 --> 30:16.100
The great human trial occurred
in July 1885,

30:16.098 --> 30:18.628
with a famous case of a
nine-year-old boy,

30:18.630 --> 30:22.790
Joseph Meister,
who had been severely bitten by

30:22.785 --> 30:28.205
a rabid dog and was thought to
be certain to die an agonizing

30:28.205 --> 30:29.105
death.

30:29.108 --> 30:34.098
But taking advantage of the
incubation period for rabies,

30:34.102 --> 30:39.632
Pasteur vaccinated the boy with
his attenuated rabies virus.

30:39.630 --> 30:44.030
Joseph Meister survived,
and became a celebrity patient,

30:44.026 --> 30:48.416
the first person ever known to
have survived after being

30:48.422 --> 30:51.462
severely bitten by a rabid
animal.

30:51.460 --> 30:54.960
And Meister remained loyal for
the rest of his life,

30:54.958 --> 30:55.848
to Pasteur.

30:55.848 --> 30:57.638
He returned,
as an adult,

30:57.644 --> 31:01.164
to Paris, to work as a
gatekeeper at the Pasteur

31:01.157 --> 31:05.717
Institute, where Pasteur himself
was buried in the crypt.

31:05.720 --> 31:10.350
The apocryphal story--I won't
assert its truth--

31:10.348 --> 31:12.938
the story is that he was killed
in 1940,

31:12.940 --> 31:16.180
as an elderly man,
when he tried to prevent

31:16.183 --> 31:20.823
occupying German troops from
desecrating Pasteur's grave,

31:20.818 --> 31:26.868
the grave of a national icon of
an enemy power.

31:26.868 --> 31:31.688
A slightly less poignant but
better documented narrative is

31:31.694 --> 31:35.774
that he committed suicide in
despair of the German

31:35.771 --> 31:37.021
occupation.

31:37.019 --> 31:41.819
Well, the Pasteur
Institute--that's the

31:41.824 --> 31:45.874
vaccination of Joseph Meister.

31:45.868 --> 31:49.398
It's not Pasteur doing the
actual vaccination,

31:49.404 --> 31:52.864
because, as I said,
he wasn't a physician.

31:52.858 --> 31:55.788
And this is the Pasteur
Institute,

31:55.788 --> 31:59.748
founded in 1887,
with Louis Pasteur himself as

31:59.751 --> 32:03.661
its first director,
committed to biomedical

32:03.657 --> 32:07.397
research in Paris,
and to a series of satellite

32:07.404 --> 32:09.954
institutes elsewhere in the
world.

32:09.950 --> 32:15.670
It followed the public health
strategy of vaccination,

32:15.666 --> 32:20.306
pioneered by Jenner,
and now consolidated by

32:20.305 --> 32:21.595
Pasteur.

32:21.598 --> 32:25.048
The founding of this
institute--you'll note its size

32:25.051 --> 32:28.871
and imposing nature--
gives us the opportunity to

32:28.865 --> 32:33.625
note in passing another aspect
of nineteenth and twentieth

32:33.631 --> 32:35.221
century science.

32:35.220 --> 32:38.910
The way in which it became a
focal point for competing

32:38.913 --> 32:41.773
nationalisms,
in a way familiar to us from

32:41.771 --> 32:44.911
the Cold War competition between
the U.S.

32:44.910 --> 32:46.850
and the USSR.

32:46.848 --> 32:49.748
In any case,
there's a clear case in the

32:49.748 --> 32:53.908
nineteenth century with the
rivalry between Louis Pasteur

32:53.909 --> 32:57.689
and Robert Koch,
the embodiments and icons of

32:57.688 --> 33:00.538
French and German medical
science,

33:00.539 --> 33:04.419
of two hostile national powers.

33:04.420 --> 33:10.510
The Pasteur Institute in Paris
rivaled the Koch Institute in

33:10.509 --> 33:11.439
Berlin.

33:11.440 --> 33:16.630
And that brings us--we'll also
note the crypt where Pasteur is

33:16.625 --> 33:17.385
buried.

33:17.390 --> 33:24.800
There's a kind of--what shall I
say?--worship of Pasteur almost,

33:24.797 --> 33:28.557
and of French medical science.

33:28.558 --> 33:34.328
But let's move on to Robert
Koch, who lived from 1843 to

33:34.329 --> 33:37.539
1910,
the second great figure in the

33:37.538 --> 33:41.168
establishment of the germ theory
of disease,

33:41.170 --> 33:45.810
the German scientist who was
twenty years younger than

33:45.805 --> 33:46.675
Pasteur.

33:46.680 --> 33:52.490
Now, if Pasteur's hallmark was
the imaginative breadth of his

33:52.493 --> 33:57.523
scientific vision,
Koch's distinctive feature was

33:57.518 --> 34:03.048
his scientific rigor,
his more rigorous techniques of

34:03.054 --> 34:04.524
microbiology.

34:04.519 --> 34:08.319
He had a critique,
a famous critique,

34:08.322 --> 34:12.762
of the whole swan neck flask
experiment.

34:12.760 --> 34:19.090
He argued that Pasteur had been
lucky--contamination was

34:19.085 --> 34:20.345
possible.

34:20.349 --> 34:24.539
He developed the plate
technique, using the Petri dish

34:24.543 --> 34:27.953
and solid culture,
and he developed staining

34:27.945 --> 34:30.315
techniques for microscopy.

34:30.320 --> 34:35.110
What I'd particularly like you
to note is his methodology,

34:35.114 --> 34:39.154
which he embodied in what are
called "Koch's

34:39.152 --> 34:40.922
Postulates."

34:40.920 --> 34:45.640
This was the methodology for
determining that a suspected

34:45.641 --> 34:50.451
microbe is the causative agent
of a particular disease.

34:50.449 --> 34:53.749
He said you could know this
under four conditions.

34:53.750 --> 34:58.810
First, the organism suspected
as a pathogen must be found in

34:58.806 --> 35:02.316
all animals suffering from the
disease.

35:02.320 --> 35:05.030
In other words,
it has to be universally

35:05.030 --> 35:07.740
present where the disease is
present.

35:07.739 --> 35:13.529
And then the organism must be
isolated from a diseased animal,

35:13.527 --> 35:15.707
and grown in culture.

35:15.710 --> 35:20.560
Third, the cultured organism
must cause the disease,

35:20.563 --> 35:24.373
when introduced into a healthy
animal.

35:24.369 --> 35:29.289
And lastly, the organism must
be re-isolated from the

35:29.293 --> 35:32.423
experimentally infected animal.

35:32.420 --> 35:38.270
These postulates are some of
the most famous in medical

35:38.266 --> 35:44.976
science, and were the model for
establishing germs as pathogens

35:44.978 --> 35:47.468
for other diseases.

35:47.469 --> 35:53.459
Koch's microscopy had a number
of immediate implications.

35:53.460 --> 35:57.710
His staining raised the idea
that if you could stain,

35:57.708 --> 36:01.298
you could also have an idea of
magic bullets,

36:01.302 --> 36:04.082
what later became antibiotics.

36:04.079 --> 36:09.529
But Koch didn't pursue that
particular interest.

36:09.530 --> 36:15.130
The other was this led to
reliable differential diagnosis,

36:15.125 --> 36:19.735
and therefore a more properly
based nosology.

36:19.739 --> 36:23.559
It could lead also to major
public health measures,

36:23.563 --> 36:27.313
and ultimately to developments
in therapeutics.

36:27.309 --> 36:30.889
It furthered the sanitary idea,
and gave it a firm,

36:30.889 --> 36:36.379
scientific basis,
and irrefutably proved the

36:36.378 --> 36:43.268
truth of contagionism rather
than anticontagionism,

36:43.268 --> 36:47.178
as Pettenkofer learned,
to his cost.

36:47.179 --> 36:50.209
But immediately there
wasn't--it didn't imply,

36:50.210 --> 36:54.000
and I think we should note
this--the understanding of

36:53.998 --> 36:58.298
disease did not immediately lead
to therapeutic advances.

36:58.300 --> 37:03.100
Remember what happened in
Naples during the cholera of

37:03.096 --> 37:03.726
1884.

37:03.730 --> 37:09.830
Koch's idea was used for a very
negative therapeutic method;

37:09.829 --> 37:15.209
that is, acid enemas that were
administered to patients.

37:15.210 --> 37:20.340
Well Koch also moved forward on
other diseases,

37:20.340 --> 37:22.890
applying the methods he had
developed,

37:22.889 --> 37:26.169
that Pasteur had developed in
the 1870s,

37:26.170 --> 37:30.550
and applying his own rigorous
postulates.

37:30.550 --> 37:38.600
In 1882, the most famous of
all, he isolated the bacterium

37:38.597 --> 37:46.217
that causes tuberculosis,
the most prevalent disease of

37:46.224 --> 37:48.064
the time.

37:48.059 --> 37:52.409
The paper that Koch presented
in 1882 was one of the most

37:52.414 --> 37:57.084
dramatic and important moments
in the history of medicine.

37:57.079 --> 38:01.119
Tuberculosis was not feared in
the same way cholera was,

38:01.119 --> 38:04.029
but it was unquestionably the
greatest killer of the

38:04.025 --> 38:06.745
nineteenth century,
and until 1882,

38:06.751 --> 38:09.501
it was shrouded in mystery.

38:09.500 --> 38:15.760
Suddenly Koch cast a new shaft
of life, revealing to the world

38:15.762 --> 38:21.822
that he had unraveled the entire
mystery of its etiology.

38:21.820 --> 38:24.960
Then, in 1883,
he followed up this discovery

38:24.958 --> 38:28.678
with another that was almost
equally influential.

38:28.679 --> 38:33.959
In 1883, he isolated the
Vibrio cholerae.

38:33.960 --> 38:38.980
Koch then had discovered and
demonstrated the role of

38:38.983 --> 38:42.733
pathogens,
the ones responsible for two of

38:42.733 --> 38:47.483
the most prevalent and feared
nineteenth century diseases.

38:47.480 --> 38:51.430
This marked,
as I said, the definitive

38:51.425 --> 38:54.195
triumph of contagionism.

38:54.199 --> 38:59.059
And the 1880s and '90s were a
golden age of microbiology,

38:59.063 --> 39:03.843
with the pathogens being
discovered for a whole range of

39:03.838 --> 39:05.488
other diseases.

39:05.489 --> 39:09.629
This was an extraordinary
period in medical science.

39:09.630 --> 39:13.350
The pathogens were discovered
for gonorrhea,

39:13.347 --> 39:16.287
bubonic plague,
dysentery, tetanus,

39:16.286 --> 39:21.466
the common bacteria of wound
infections, staph infections and

39:21.474 --> 39:22.604
others.

39:22.599 --> 39:26.499
The paradox,
of course, there were still few

39:26.503 --> 39:30.773
benefits for patients,
until the turn of the new

39:30.769 --> 39:31.859
century.

39:31.860 --> 39:35.340
The quip was made that the main
beneficiaries,

39:35.344 --> 39:40.154
at first, of the germ theory of
disease, were physicians rather

39:40.146 --> 39:41.536
than patients.

39:41.539 --> 39:44.899
But there was a major
exception, and that was not in

39:44.898 --> 39:46.608
medicine but in surgery.

39:46.610 --> 39:51.080
And this introduces the third
major figure of our trio,

39:51.079 --> 39:53.579
establishing the germ theory of
disease,

39:53.579 --> 39:59.159
and that's Joseph Lister,
who lived from 1827 to 1912,

39:59.159 --> 40:02.629
and made his major
contributions in Scotland.

40:02.630 --> 40:06.240
He was professor of surgery at
Edinburgh University,

40:06.240 --> 40:10.210
where he was appalled by the
numbers of patients who died

40:10.206 --> 40:13.176
after otherwise successful
operations.

40:13.179 --> 40:17.409
You know the old joke about the
operation being successful,

40:17.407 --> 40:19.737
just too bad the patient died.

40:19.739 --> 40:24.749
Well, Pasteur's idea
immediately struck him for its

40:24.751 --> 40:28.461
lifesaving, practical
implications.

40:28.460 --> 40:33.530
That is, he made practical use
of Pasteur's discovery about the

40:33.532 --> 40:37.792
role of airborne germs in
causing wound infections in

40:37.788 --> 40:38.768
surgery.

40:38.768 --> 40:41.108
Now, surgery,
before Lister,

40:41.106 --> 40:43.786
had a number of major limits.

40:43.789 --> 40:48.489
There was pain itself,
and the need for speed.

40:48.489 --> 40:53.249
There was blood loss,
and there was septicemia.

40:53.250 --> 40:57.480
The result was that the major
body cavities remained off

40:57.481 --> 41:01.251
limits: the abdominal cavity,
the thoracic cavity,

41:01.250 --> 41:03.020
the cranial cavity.

41:03.018 --> 41:07.118
And there was a high rate of
death from infection.

41:07.119 --> 41:11.709
The idea was thought by
physicians at the time that the

41:11.711 --> 41:15.881
infection arose through
spontaneous generation.

41:15.880 --> 41:19.680
As tissue died,
they gave off toxins that

41:19.681 --> 41:23.871
caused infection,
and so infection was simply

41:23.865 --> 41:28.995
accepted as an inevitable,
normal part of surgery.

41:29.000 --> 41:32.360
Lister's surgical revolution
occurred with the work he

41:32.364 --> 41:35.114
published,
"On the Antiseptic

41:35.114 --> 41:38.634
Principle in the Practice of
Surgery,"

41:38.628 --> 41:39.548
in 1864.

41:39.550 --> 41:43.700
The implications of Pasteur's
work on fermentation were

41:43.704 --> 41:46.324
that--you could have an analogy.

41:46.320 --> 41:49.260
If Pasteur was right,
there was no spontaneous

41:49.260 --> 41:50.110
generation.

41:50.110 --> 41:54.990
An airborne microorganism
penetrated the wound and caused

41:54.985 --> 41:57.245
infection or septicemia.

41:57.250 --> 42:01.930
The remedy was to prevent the
penetration of the

42:01.932 --> 42:05.922
microorganism,
the idea of antisepsis.

42:05.920 --> 42:11.130
So, Lister accepted Pasteur's
insight that infections were not

42:11.126 --> 42:15.216
a chemical reaction,
caused by oxidation when air

42:15.222 --> 42:16.932
touched a wound.

42:16.929 --> 42:20.529
Instead, infection was the
result of contamination,

42:20.532 --> 42:24.212
from the outside,
of the wound by microorganisms.

42:24.210 --> 42:29.770
His solution first was this,
the carbolic spray device that

42:29.768 --> 42:31.108
he invented.

42:31.110 --> 42:35.720
What you did was to spray the
air around the patient,

42:35.715 --> 42:40.315
applying carbolic acid also
directly to the wound.

42:40.320 --> 42:44.970
And Lister also washed his
hands before operating,

42:44.974 --> 42:48.114
and sterilized his instruments.

42:48.110 --> 42:54.920
There's a stylized idea of a
Lister-type surgical technique

42:54.916 --> 42:56.086
at work.

42:56.090 --> 42:59.200
Well, until Lister's
revolutionary innovation,

42:59.197 --> 43:03.127
surgery had been an emergency,
a treatment of last resort,

43:03.132 --> 43:05.552
because of the wound infection.

43:05.550 --> 43:10.810
After 1866, it became a normal
procedure.

43:10.809 --> 43:14.269
There were other innovations as
well, that went with it.

43:14.268 --> 43:16.838
His contemporaries improved on
Lister.

43:16.840 --> 43:19.820
You'll see that here they
aren't wearing masks,

43:19.822 --> 43:21.382
for example,
or gowns.

43:21.380 --> 43:25.120
Those are introduced--and
gloves made from vulcanized

43:25.119 --> 43:27.899
rubber--
were introduced in the 1890s,

43:27.896 --> 43:31.866
but really became a part of
best practice only from about

43:31.867 --> 43:34.347
the time of the First World War.

43:34.349 --> 43:37.919
This also revolutionalized
obstetrics,

43:37.920 --> 43:41.300
with the conquest of puerperal
fever,

43:41.300 --> 43:46.130
with--hospital and clinical
procedures then were transformed

43:46.125 --> 43:48.165
by the antiseptic idea.

43:48.170 --> 43:53.010
So, by the 1890s,
you have the consolidation of

43:53.012 --> 43:58.802
the germ theory of disease,
revolutionalizing medicine and

43:58.797 --> 44:03.257
become accepted throughout the
international medical

44:03.262 --> 44:04.492
profession.

44:04.489 --> 44:10.319
I'd like to mention the impact
also on culture.

44:10.320 --> 44:16.450
And this particular book,
which is by Bram Stoker,

44:16.449 --> 44:21.929
which is Dracula,
published in 1897,

44:21.929 --> 44:25.229
that gives us,
I would argue,

44:25.226 --> 44:29.816
expression in a really dramatic
and--

44:29.820 --> 44:32.080
I just read it again--a really
scary--

44:32.079 --> 44:41.029
I assure you--idea of anxieties
about infection.

44:41.030 --> 44:46.300
Now, Dracula is really,
for its time,

44:46.298 --> 44:48.748
a high-tech novel.

44:48.750 --> 44:52.850
In it you see all about the
latest scientific and medical

44:52.853 --> 44:54.543
inventions and ideas.

44:54.539 --> 44:58.359
It contains the phonograph,
the telephone,

44:58.360 --> 45:01.900
stenography,
railroads, the two-wheeled

45:01.900 --> 45:03.020
bicycle.

45:03.018 --> 45:07.158
And in medicine it deals with
the latest inventions in

45:07.161 --> 45:10.521
psychiatry, in blood
transfusion, infectious

45:10.523 --> 45:11.543
diseases.

45:11.539 --> 45:15.539
And indeed, I would argue,
it also involves what was the

45:15.543 --> 45:19.623
cutting edge scientific idea in
medicine at the time,

45:19.619 --> 45:24.629
the possibility of vector borne
diseases like malaria and

45:24.626 --> 45:25.606
filarial.

45:25.610 --> 45:30.780
Then it's just at the time when
we're going to see tropical

45:30.780 --> 45:32.970
medicine--
we'll look at next

45:32.965 --> 45:36.685
time--becomes the cutting edge
of late nineteenth-century,

45:36.690 --> 45:39.620
early twentieth-century medical
science.

45:39.619 --> 45:42.049
Now, you know the drill about
Dracula,

45:42.050 --> 45:45.330
how Count Dracula--the word
Dracula comes from the

45:45.326 --> 45:48.966
Romanian word dracul,
which means a devil,

45:48.967 --> 45:50.427
a little devil.

45:50.429 --> 45:55.429
And you know how he lived,
the Count--the evil Count--in

45:55.429 --> 45:59.249
Transylvania,
in Romania, in the Carpathian

45:59.246 --> 46:00.516
Mountains.

46:00.518 --> 46:05.908
And the important point is he
travels by ship from the Black

46:05.913 --> 46:09.093
Sea port,
aboard a Russian vehicle,

46:09.094 --> 46:14.744
through the Mediterranean,
and up along the coast of Spain

46:14.740 --> 46:18.230
and France,
where he lands by ship in

46:18.231 --> 46:20.841
Britain at the port of Whitby.

46:20.840 --> 46:26.300
Then he travels by train,
and is transported by railroad

46:26.295 --> 46:31.545
from Whitby to London,
where his plan is to ravage the

46:31.552 --> 46:34.532
huge population of London.

46:34.530 --> 46:36.320
Now, what does that remind you
of?

46:36.320 --> 46:40.060
Doesn't that--it reminds
me--I'm going to argue that

46:40.061 --> 46:42.411
Dracula is many things.

46:42.409 --> 46:46.959
In literature,
you'll see that Dracula

46:46.963 --> 46:53.383
is a metaphor--and this is often
said--for repressed sexuality,

46:53.382 --> 46:55.972
in the Victorian Era.

46:55.969 --> 47:01.829
You'll find interpretations of
it as expressing also a

47:01.826 --> 47:04.696
repressed homoeroticism.

47:04.699 --> 47:09.159
In it, we also find expression
of the battle of good and evil.

47:09.159 --> 47:13.449
That's our friend Dracula.

47:13.449 --> 47:17.929
And you'll see--love never
dies--the idea of--the sexual

47:17.931 --> 47:21.841
idea is clearly--some 200 films
have been made of

47:21.840 --> 47:23.390
Dracula.

47:23.389 --> 47:28.859
And you can see clearly
possible sexual ideas in films

47:28.860 --> 47:30.410
such as this.

47:30.409 --> 47:32.739
And they're clearly also here.

47:32.739 --> 47:36.589
But what I want to argue is
what's been neglected so often--

47:36.590 --> 47:40.190
and I think it's really
important--is I want to argue

47:40.188 --> 47:44.618
that Dracula is also an
allegory of infectious disease;

47:44.619 --> 47:48.529
not a specific disease,
but diseases like plague and

47:48.534 --> 47:51.184
cholera,
that originated in Eastern

47:51.177 --> 47:54.797
Europe and traveled,
just as Dracula did,

47:54.797 --> 47:59.677
by ship and by railroad;
that they had Count Dracula's

47:59.682 --> 48:04.212
goal of ravaging industrial
cities, huge population centers

48:04.208 --> 48:05.378
like London.

48:05.380 --> 48:10.480
And it's interesting that the
vampire hunters in the novel are

48:10.480 --> 48:14.740
doctors, physicians,
whose mission is to destroy the

48:14.744 --> 48:16.504
invading vampire.

48:16.500 --> 48:20.030
Also involved,
we see, is the seasonality.

48:20.030 --> 48:23.640
It's not by chance that Count
Dracula arrives in late

48:23.643 --> 48:26.703
August/September,
just as cholera would have,

48:26.701 --> 48:28.231
or bubonic plague.

48:28.230 --> 48:32.520
And we see miasmatism in the
novel: the flowers,

48:32.516 --> 48:36.526
the garlic, the mists
surrounding Dracula.

48:36.530 --> 48:40.180
And I would argue that Dracula
is a composite of many

48:40.177 --> 48:41.087
infections.

48:41.090 --> 48:43.690
Here's the handsome count again.

48:43.690 --> 48:47.980
And I'd like to show you one
more handsome picture of him;

48:47.980 --> 48:49.670
and that's that one.

48:49.670 --> 48:54.850
And I would argue that this
clearly makes me think also of

48:54.849 --> 48:59.709
vector-borne disease,
and possibly this is a million

48:59.713 --> 49:03.473
miles removed from malaria and
filarial,

49:03.469 --> 49:05.879
which we'll be talking about
next week.

49:05.880 --> 49:09.530
So, I urge you also to read
Dracula.

49:09.530 --> 49:12.020
I'm sure you'll enjoy it as
much as I did.

49:12.019 --> 49:16.999