WEBVTT

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Prof: I want to turn to
the next topic,

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which marks a new unit in our
course.

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That is to say,
until now we've dealt with

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bubonic plague,
in a series of talks and in

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your first section meeting.

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Now I'd like to look,
for comparative purposes,

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at a very different high-impact
disease;

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and this time and next we'll be
dealing with smallpox.

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So, I think you deserve an
answer to the obvious questions:

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why smallpox,
and why at this stage in the

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course?

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So, I want to give you a little
bit of explanation,

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to see where we're going.

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The first has to do with I
might call a varied intellectual

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diet,
and I want us to deal with

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diseases of very different
types,

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and so we'll have to examine
the impact of different kinds of

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infectious diseases.

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Plague was a bacterial disease.

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Smallpox instead is viral.

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Plague was transmitted by
vectors.

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You know the drill now,
the role of rats and fleas.

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Smallpox instead is spread by
contact and airborne inhalation

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of droplets.

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Plague is a classic epidemic
disease, in the sense that it's

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an outside invader that ravages
a locality for a season and then

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departs.

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Smallpox is different in that
it can be both endemic and

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epidemic.

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So, we'll see a different
dynamic.

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It's also true that the social
responses to smallpox were quite

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different.

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Plague was associated with
terror and social disruption,

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and in the New World we'll see
that it had an even more

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dramatic impact on the Native--
smallpox did--on the Native

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American population.

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But in European conditions it
was a familiar endemic disease

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with a less dramatic--
as a cause--was less dramatic

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as a cause of social tensions
and disruption.

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We'll see too that in terms of
impact, for chronology it makes

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sense to look at smallpox at
this stage in our class.

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It had long been present in
human history,

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but there was an upsurge in
smallpox in the seventeenth and

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eighteenth centuries that
accompanied the surge in the

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demography of Europe.

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And it also reflected the
transformation of social and

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economic conditions associated
with the commercialization of

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agriculture,
the onset of industrial

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development,
and rapid, unplanned

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urbanization,
with those associated

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pathologies such as
overcrowding,

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both at home and in the
workplace.

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In those conditions,
smallpox was a great killer,

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and it succeeded plague as the
most dreaded disease of the

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late-seventeenth and the
eighteenth century.

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In a sense, we're moving from
bubonic plague,

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the most dreaded disease of its
era,

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to--in a sense,
in terms of fear--to smallpox

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as the next most dreaded disease
of the next period in the

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eighteenth century.

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But there's more to it that
that.

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Smallpox, as you'll see in our
reading and in our lecture next

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time, was also extraordinarily
important in terms of its impact

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in the New World.

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It led to a demographic
catastrophe for the Native

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American population,
largely spontaneously,

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but there were also intentional
acts of genocide involved.

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So, we're going to see,
in terms of one of the themes

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of our course,
that disease,

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and particularly smallpox,
played an important role in the

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big picture of history;
in conditioning or creating

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factors that were important in
European settlement in the New

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World,
and that led to the

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introduction of African slavery,
as the Native American

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population had no immunity and
perished from smallpox,

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and therefore could not be
enslaved;

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whereas Africans,
possessing immunity,

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were imported to replace them.

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Another major feature and
reason for dealing with smallpox

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has to do with another theme of
our course, and that is public

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health.

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We've already dealt with plague
measures of public health.

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You know what they are,
the plague measures:

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boards of health,
quarantine, lazarettos,

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sanitary cordons,
emergency burial regulations.

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Smallpox, by contrast,
was to lead to a very different

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but highly effective style of
public health;

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that is, first inoculation and
then vaccination,

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associated with Edward Jenner.

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Even more spectacularly than
plague measures,

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vaccination ultimately promoted
a victory over smallpox,

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leading in 1980 to its total
global eradication,

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at least naturally occurring
smallpox;

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the first, and still as we
speak, the only human disease to

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be so intentionally eradicated.

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Unlike plague measures,
vaccination was a powerful tool

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of public health.

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Successful vaccines have
subsequently been developed

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against other diseases:
measles, rubella,

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whooping cough,
tetanus, diphtheria,

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rabies, polio.

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But again, like plague
measures, vaccines have been

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controversial--
and we'll be talking about when

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vaccines form an appropriate
strategy--

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and eradication has been ever
more elusive for diseases other

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than smallpox.

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It may be that smallpox is a
special case,

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rather than,
as many hoped,

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a model for the eradication of
diseases sequentially,

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one after another.

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We'll be looking also at
smallpox because of its

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demographic and economic
effects.

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We talked, in terms of plague,
of a mortality revolution,

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in terms of demography,
and also of its impact on

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industrialization.

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Smallpox and the successful
containment of smallpox through

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inoculation and vaccination also
had a major impact on that

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mortality revolution,
and therefore also on economic

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development.

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We'll be looking also at
cultural impact,

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and we'll see that smallpox
also produced the cult of

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certain new saints;
that it too became a theme in

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the arts and literature.

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More speculatively,
we talked last time about the

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possible relationship of the
successful conquest of plague on

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the coming of the Enlightenment.

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Well, smallpox provides us with
a second instance of the

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successful deployment of human
means to control a major cause

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of death and anguish,
making life more secure and

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longer.

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It's suggested that a number of
leading philosophes were

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avid proponents of inoculation,
including Voltaire and

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Condorcet.

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So, we'll be dealing with those
issues.

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But this morning what I'd like
to do is to concentrate on

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something more narrow,
which is--but forms the basis

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for our understanding of the
impact of this disease--

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its nature as a disease.

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How it affects the individual
human body, and what were the

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treatments in the seventeenth,
eighteenth centuries.

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Let's begin with smallpox as a
disease.

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Smallpox, often nicknamed,
for reasons we'll soon see,

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"the speckled
monster."

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It's a virus belonging to the
family of orthopox viruses that

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includes Variola major,
Variola minor and

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cowpox.

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We'll talk about cowpox next
time, because of its influence

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in the development of
vaccination.

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But our theme will concern
Variola major and

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Variola minor;
especially Variola

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major, which is the
causative agent,

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primarily, of smallpox.

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This is a picture of Variola
major, the largest of all

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viruses, first seen by the
microscope in 1905.

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This causes classical smallpox.

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There's Variola minor as
well, that first appeared in the

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twentieth century;
and for our purposes we can

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afford to ignore it.

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It was of minor impact and now,
like Variola major,

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it's extinct as well.

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Now, one question is,
what's a virus?

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We talked about the term
microbe;

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microbe being a generic term
for microscopic organisms,

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including bacteria,
like our friend Yersinia

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pestis,
the causative agent of bubonic

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plague,
and viruses like Variola

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major and Variola
minor,

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the pathogens that cause
smallpox.

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Plague was caused by bacteria,
and those,

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as you know--and will be
studying more on Science Hill--

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are unicellular organisms that
are definitely and unequivocally

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alive.

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They reproduce by dividing.

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They contain DNA,
plus all the cellular machinery

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necessary to read it,
and to produce the many

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proteins that enable it to live
and reproduce.

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Viruses are something different.

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And here there's a possible
confusion lurking for the

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historian.

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The word "virus"
itself is ancient.

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In the humoral system,
in fact, when diseases were

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seen to arise from assaults on
the body on the outside,

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one of the major environmental
insults that was thought to lead

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to disease was the corrupted air
or miasma,

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and this was influenced by a
poison,

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that might be called a virus.

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So, if you do research on
medical history,

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you'll see the term
"virus"

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used in an old sense for many
centuries.

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But "virus"
in present medical discourse is

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a term that dates its modern
usage from the early twentieth

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century,
and it refers to parasitic

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particles,
perhaps 500 times smaller than

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bacteria.

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Their existence was established
by elegant scientific

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experiments in the first years
of the century,

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completed by about 1903.

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But they couldn't actually be
seen until the invention of

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electron microscope in the
1930s,

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and their functioning wasn't
understood until the DNA

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revolution of the 1950s.

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So, viruses,
we now know,

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consist of some of the elements
of life, stripped to their most

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basic.

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A virus really is nothing more
than a piece of genetic material

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wrapped in a protein case.

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They're particles that are
inert on their own.

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Viruses lack the machinery to
read DNA, or to make proteins,

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or carry out metabolic
processes.

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They can do nothing on their
own, and they cannot reproduce

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by themselves.

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Their survival depends instead
on invading living cells.

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Once inside,
they highjack the cell and its

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machinery.

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The genetic code of the
virus--and the virus,

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after all, is almost nothing
else--gives the cell the message

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it needs to reproduce more
virus,

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thus transforming cells into
virus producing factories,

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and in the process they destroy
the host cell.

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As they produce more and more
viruses,

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and destroy more and more
cells, the effect on the human

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body can be severe,
even catastrophic,

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depending on the capacity of
the immune system to contain or

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destroy the invasion.

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Here we have,
in a sense, the opposite of a

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Hippocratic idea of disease;
the body assaulted,

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not from the outside,
but rather from a parasitic

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pathogen deep within.

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There is an exotic debate,
of course--are viruses alive?

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Those who argue that they are
alive, note that they're capable

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of transmitting genetic
material, one of the key

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indications of life.

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Those who claim they're not
alive, note that on their own

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they're inert,
that they can't carry on

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metabolic processes,
or produce proteins.

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Viruses, they note,
are the ultimate parasites.

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Virologists often say that
whether you decide that viruses

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are alive or not is ultimately a
matter or disciplinary

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perspective,
or perhaps even personal

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preference.

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The reassuring point for us is
that, perhaps excepting

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theology, the answer doesn't
really matter.

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In any case,
what we need to know is that

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smallpox was caused by a virus,
and a virus that has no animal

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reservoir.

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The disease was restricted
entirely to human beings,

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and that will prove to be
important in making it

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eventually a good candidate for
eradication.

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The name for the virus,
Variola,

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derives from the Latin
varius,

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meaning spotted.

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And in England the disease,
in fact, was popularly called,

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as I've said,
"the speckled

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monster."

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So, here's a picture of the
smallpox virus--oops,

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it's gone out;
there it is.

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And that's a schematic image of
a smallpox virus.

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And as I said,
there is a mutation that

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occurred in the twentieth
century, causing the rise of

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Variola minor,
as well as Variola

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major.

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But we'll be concerned
exclusively here with Variola

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major;
the main cause of smallpox

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historically.

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Well, how was it transmitted?

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Here we need to remember that
smallpox is an exceedingly

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contagious disease.

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A smallpox patient sheds
millions of infective viruses

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into his or her immediate
surroundings,

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from the rash and from the open
sores in the sufferer's throat.

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The patient is infective from
just before the onset of the

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rash until the very last scab
falls off weeks later.

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Not everyone,
of course, who is exposed is

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infected.

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Living along with people with
immunity--

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and leaving that aside--it has
been estimated that the chances

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are about 50:50 that a
susceptible member of a

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household would contract
smallpox from an ill patient in

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the home.

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The dominant manner to spread
smallpox was by contact

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infection,
droplets breathed out in

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face-to-face contact with a
susceptible person and inhaled

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by that person.

18:03.740 --> 18:08.890
Normally the spread was in the
context of intense contact over

18:08.894 --> 18:12.494
a period of time;
that is, a family member,

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or someone on a hospital ward,
in an enclosed workplace--an

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office,
a factory, a mine--a school

18:19.682 --> 18:24.032
classroom,
an army barrack, a refugee camp.

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And it's most easily
transmitted in dry,

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cool seasons.

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That's the primary mode of
transmission.

18:35.279 --> 18:40.179
There are two more,
however, that are more

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relatively secondary.

18:42.930 --> 18:48.270
A second mode of transmission
is by what are called--another

18:48.266 --> 18:50.976
bit of jargon here--fomites.

18:50.980 --> 18:55.620
A fomite is simply an inanimate
object, capable of carrying

18:55.618 --> 18:59.538
infectious material from one
person to another.

18:59.538 --> 19:03.658
Examples might be bed linen,
clothing;

19:03.660 --> 19:08.690
the shroud from an infected
person that transmits viruses

19:08.694 --> 19:13.284
from one body--that is,
of the sufferer--to the next

19:13.279 --> 19:14.269
person.

19:14.269 --> 19:18.829
Other examples are simply
doorknobs, eating utensils,

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and so on.

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So, that's a second mode of
transmission.

19:22.798 --> 19:26.668
There's a third too,
that smallpox can be vertically

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transmitted;
that is, from mother to infant.

19:31.930 --> 19:37.450
It's possible for an infant to
be born with congenital

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smallpox.

19:38.598 --> 19:42.358
Well, that's the mode of
transmission.

19:42.359 --> 19:45.729
What about its epidemiology?

19:45.730 --> 19:51.810
Well, some favoring factors
include large urban populations.

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It's not coincidental that
smallpox raged in Western Europe

19:57.259 --> 19:59.889
in the eighteenth century.

19:59.890 --> 20:04.980
The crowded living conditions
and workplaces were ideal for

20:04.980 --> 20:06.650
its transmission.

20:06.650 --> 20:10.640
Trade and the movement of
people, displaced people,

20:10.641 --> 20:11.441
warfare.

20:11.440 --> 20:16.130
People who assembled and
reassembled in crowds were ideal

20:16.133 --> 20:18.483
for transmitting smallpox.

20:18.480 --> 20:22.980
The disease is known to have
afflicted Ancient Egypt.

20:22.980 --> 20:28.700
Mummies are known to have been
victims of smallpox.

20:28.700 --> 20:33.240
But the important point is that
it became endemic in Europe,

20:33.240 --> 20:36.680
that became the world reservoir
of infection,

20:36.680 --> 20:39.700
from which it spread by trade,
colonization,

20:39.700 --> 20:41.690
warfare.

20:41.690 --> 20:44.900
And in European cities it
became, above all,

20:44.902 --> 20:46.772
a disease of childhood.

20:46.769 --> 20:52.079
But about a third of the deaths
of children in the seventeenth

20:52.079 --> 20:54.779
century were due to smallpox.

20:54.779 --> 20:58.689
So, a reason then for dealing
with smallpox now,

20:58.694 --> 21:01.944
in our course,
is that it was on a major

21:01.943 --> 21:06.613
upsurge in the seventeenth and
eighteenth centuries.

21:06.609 --> 21:07.919
How was it named?

21:07.920 --> 21:10.390
Why is it called smallpox?

21:10.390 --> 21:11.190
A small point.

21:11.190 --> 21:15.140
But we need to know that it's
from a comparative description

21:15.137 --> 21:17.277
of its characteristic lesions.

21:17.278 --> 21:20.348
The "great pox"
is a disease which we'll be

21:20.346 --> 21:23.806
dealing with pretty soon,
which was syphilis,

21:23.805 --> 21:28.265
that creates large lesions and
affects adults.

21:28.269 --> 21:35.299
The smallpox had small lesions
and primarily affected children;

21:35.298 --> 21:39.458
at least in countries in which
it was endemic.

21:39.460 --> 21:44.370
Another point we should know
about smallpox is that after

21:44.372 --> 21:48.672
infection, a person enjoys a
lifelong immunity.

21:48.670 --> 21:52.950
We need to know that because
it's a major factor in the

21:52.948 --> 21:57.938
public health measures that the
disease eventually generated.

21:57.940 --> 21:59.810
Well, what about its symptoms?

21:59.808 --> 22:04.118
How does it affect the
individual human body?

22:04.118 --> 22:09.078
After inhaling the virus,
there's an incubation period,

22:09.083 --> 22:13.683
which normally lasts something
like twelve days.

22:13.680 --> 22:18.140
This is important in its
epidemiology because it allowed

22:18.138 --> 22:22.928
the spread of the disease;
because an infected person had

22:22.932 --> 22:27.812
ample time to travel before
falling ill, and therefore time

22:27.809 --> 22:32.519
to take the disease with him or
her and to spread it.

22:32.519 --> 22:37.039
Now, I'm going to give some
attention--perhaps more than you

22:37.040 --> 22:41.100
might like when you see the
images--to the symptoms of

22:41.103 --> 22:42.103
smallpox.

22:42.099 --> 22:44.619
And there's a reason for that.

22:44.618 --> 22:48.618
Part is that smallpox is
tremendously,

22:48.621 --> 22:52.191
terribly, terrifyingly painful.

22:52.190 --> 22:55.450
Plus it leads--and this is
important too,

22:55.450 --> 22:58.640
in the way that it impacted
society--

22:58.640 --> 23:02.080
it often produces lifelong
scarring,

23:02.078 --> 23:07.988
disfiguring and blindness,
and these in turn spread fear

23:07.988 --> 23:10.028
of it and terror.

23:10.028 --> 23:15.938
And, so, the very word smallpox
has a particular resonance in

23:15.943 --> 23:20.383
popular imagination,
associated with dread.

23:20.380 --> 23:23.940
People sometimes ask,
in a course like this,

23:23.942 --> 23:28.752
which of the diseases we
encounter was really the worst?

23:28.750 --> 23:33.430
The question doesn't permit
empirical verification,

23:33.430 --> 23:36.750
because no one has ever
suffered, mercifully,

23:36.750 --> 23:41.430
all the afflictions we study
and had the opportunity to

23:41.432 --> 23:42.302
compare.

23:42.298 --> 23:46.898
But it is meaningful to note
the impression of those who

23:46.895 --> 23:51.825
lived through the times when
smallpox claimed its legions of

23:51.827 --> 23:52.827
victims.

23:52.828 --> 23:55.728
They thought--and the
physicians who treated

23:55.732 --> 23:59.382
them--that smallpox was the
worst of human maladies;

23:59.380 --> 24:02.860
that was a term that was said
at the time.

24:02.858 --> 24:05.348
And this, in fact,
was the view,

24:05.351 --> 24:08.971
closer to home,
of the Illinois State Board of

24:08.968 --> 24:11.378
Health in 1902,
where Dr.

24:11.380 --> 24:16.690
Donald Hopkins wrote this:
"In the suddenness and

24:16.692 --> 24:22.672
unpredictability of its attack,
in the grotesque torture of its

24:22.670 --> 24:26.490
victims,
in the brutality of its lethal

24:26.493 --> 24:31.873
or disfiguring outcome,
and in the dread that it

24:31.865 --> 24:35.815
inspired, smallpox is the worst.

24:35.818 --> 24:40.168
It's unique among human
diseases."

24:40.170 --> 24:45.260
To the extent that that's true,
it's also one of the reasons

24:45.259 --> 24:49.739
that smallpox appeals to the
malevolent as a possible

24:49.743 --> 24:52.163
instrument of bioterror.

24:52.160 --> 24:56.630
It's well-known that a major
outbreak of smallpox would

24:56.625 --> 24:59.265
spread death,
maximize suffering,

24:59.271 --> 25:04.401
and lead to widespread fear,
flight and social disruption.

25:04.400 --> 25:09.340
The symptoms are important to
examine as an integral part of

25:09.335 --> 25:10.585
this disease.

25:10.588 --> 25:13.978
And more generally,
unless we appreciate the

25:13.982 --> 25:18.642
distinctive symptoms of each of
the diseases we examine,

25:18.640 --> 25:23.180
there's a distorting temptation
to allow them to run together,

25:23.180 --> 25:27.260
the diseases,
as so many interchangeable

25:27.263 --> 25:31.313
causes of death;
a point of view that prevents

25:31.314 --> 25:36.024
us from understanding that each
of these epidemic diseases had a

25:36.017 --> 25:38.777
distinctive and different
imprint.

25:38.779 --> 25:43.569
Smallpox was the disease that
it was, in part because of the

25:43.568 --> 25:47.928
dread that it generated;
fear not only of death,

25:47.930 --> 25:51.840
but also of exquisite
suffering, maiming,

25:51.843 --> 25:54.683
disfiguring and blindness.

25:54.680 --> 26:00.020
Only with that in mind,
can we understand why it's also

26:00.022 --> 26:05.172
so widely thought to be a
candidate for bioterror.

26:05.170 --> 26:08.160
So, we'll look at images of the
disease.

26:08.160 --> 26:13.030
And I apologize to those of you
who've just finished breakfast

26:13.026 --> 26:15.416
or just about to have lunch.

26:15.420 --> 26:19.520
In any case,
first after the incubation

26:19.518 --> 26:23.938
period, there's the pre-eruptive
stage.

26:23.940 --> 26:29.620
The virus multiplies in the
system for twelve days after

26:29.623 --> 26:34.423
incubation,
and symptoms of disease begin

26:34.423 --> 26:38.973
with a viral shower,
as the pathogen is released

26:38.970 --> 26:43.340
into the bloodstream and spreads
systemically throughout the

26:43.343 --> 26:46.413
body,
localizing eventually in the

26:46.410 --> 26:51.260
blood vessels of the skin,
just below the superficial

26:51.263 --> 26:52.023
layers.

26:52.019 --> 26:56.509
The viral load released,
and the efficiency of the

26:56.509 --> 27:01.459
body's immune response,
determine the severity and type

27:01.458 --> 27:03.198
of the disease.

27:03.200 --> 27:07.930
Onset is sudden,
with fever of 100 to 102

27:07.933 --> 27:11.843
degrees, and a general malaise.

27:11.838 --> 27:17.588
This, then, is the beginning of
perhaps a month of excruciating

27:17.586 --> 27:22.216
suffering and the danger of
spreading contagion.

27:22.220 --> 27:27.500
The early symptoms are fever,
vomiting, severe backache,

27:27.496 --> 27:32.476
splitting frontal headache,
and in children sometimes

27:32.484 --> 27:34.024
convulsions.

27:34.019 --> 27:38.339
Sometimes the disease is so
overwhelming that it leads to

27:38.338 --> 27:41.268
what's called fulminating
smallpox,

27:41.269 --> 27:44.399
which causes death within
thirty-six hours,

27:44.400 --> 27:48.040
with no outward manifestations
at all;

27:48.038 --> 27:52.228
although post-mortem exams
reveal hemorrhages in the

27:52.230 --> 27:55.930
respiratory tract,
the alimentary tract or the

27:55.930 --> 27:57.410
heart muscles.

27:57.410 --> 28:02.860
Let me give you a description
of a hyper-acute case of that

28:02.862 --> 28:03.522
kind.

28:03.519 --> 28:07.279
Physicians wrote:
"After three to four days,

28:07.278 --> 28:12.318
the patient has the general
aspect of someone who's passed

28:12.316 --> 28:15.936
through a long and exhausting
struggle.

28:15.940 --> 28:19.810
His face has lost all
expression, is mask-like,

28:19.814 --> 28:23.524
and there's a wont of tone in
all muscles.

28:23.519 --> 28:26.869
When he speaks,
this condition becomes more

28:26.868 --> 28:30.138
apparent, speaking as with
evident effort,

28:30.138 --> 28:33.328
and the voice is low and
monotonous.

28:33.328 --> 28:37.768
The patient is listless and
indifferent to surroundings.

28:37.769 --> 28:40.219
The mental attitude is similar.

28:40.220 --> 28:44.650
There's a loss of tension,
a lengthening of reaction time,

28:44.645 --> 28:46.505
and defective control.

28:46.509 --> 28:50.429
In the most fulminant cases,
the aspect of the patient

28:50.432 --> 28:54.582
resembles that of someone
suffering from severe shock and

28:54.577 --> 28:55.907
loss of blood.

28:55.910 --> 28:57.970
The face is drawn and pallid.

28:57.970 --> 29:00.990
Respiration is sighing or
gasping.

29:00.990 --> 29:05.580
The patient tosses about
continually, and cries out.

29:05.578 --> 29:09.778
His attention is fixed with
difficulty, and he complains

29:09.779 --> 29:13.039
only of agonizing pain;
now in the chest,

29:13.038 --> 29:16.848
now in the back,
the head or the abdomen."

29:16.848 --> 29:21.288
But normally smallpox wasn't
fulminant quite like that,

29:21.288 --> 29:25.278
and the patient passed on to
the next phase,

29:25.278 --> 29:30.398
which was the eruptive one,
exhibiting the classical

29:30.404 --> 29:35.334
symptoms of smallpox that led to
its diagnosis.

29:35.328 --> 29:39.878
On the third day after onset,
the patient usually felt a

29:39.875 --> 29:43.705
little better,
and in mild cases he or she

29:43.713 --> 29:46.963
could return to normal
activities,

29:46.960 --> 29:51.710
with the unfortunate effect
that this spread the disease

29:51.705 --> 29:52.565
further.

29:52.568 --> 29:56.478
But concurrently a rash
appeared;

29:56.480 --> 30:00.290
a small round or oval,
rose-colored lesion,

30:00.289 --> 30:03.189
known as a macule,
that's up to a

30:03.193 --> 30:06.373
quarter-of-an-inch in diameter.

30:06.368 --> 30:09.988
The macules appeared first on
the tongue and palate,

30:09.990 --> 30:12.760
and then, within twenty-four
hours,

30:12.759 --> 30:17.799
it spread to cover the body,
down to the palms of the hands

30:17.796 --> 30:19.876
and soles of the feet.

30:19.880 --> 30:24.090
On the cheek and forehead,
the appearance is of severe

30:24.090 --> 30:28.460
sunburn, and indeed the
sensation felt by the patient is

30:28.461 --> 30:31.641
of scalding pain or intense
burning.

30:31.640 --> 30:35.330
There's a characteristic
pattern, called centrifugal

30:35.333 --> 30:39.603
distribution;
that is, that the rash is least

30:39.597 --> 30:46.057
spread on the trunk of the body
and most densely apparent on the

30:46.057 --> 30:48.927
face and the extremities.

30:48.930 --> 30:52.770
Let me show you a slide of a
very ill little boy,

30:52.769 --> 30:57.029
and you can see this
centrifugal pattern in which the

30:57.031 --> 31:00.641
rash is most apparent on the
extremities,

31:00.640 --> 31:03.520
rather than the trunk.

31:03.519 --> 31:08.079
On day two of the rash,
a little further into the

31:08.083 --> 31:11.033
infection, the lesions alter.

31:11.028 --> 31:17.228
At this time the macule becomes
harder, and generally rises

31:17.231 --> 31:22.581
above the surface into
structures known as papules,

31:22.578 --> 31:25.358
with a flattened apex.

31:25.358 --> 31:27.348
To the touch,
they were said,

31:27.347 --> 31:30.467
by physicians,
to feel like buckshot embodied

31:30.472 --> 31:31.612
in the skin.

31:31.608 --> 31:35.408
And there we can see the
picture of a face,

31:35.406 --> 31:38.206
at that stage of the disease.

31:38.210 --> 31:43.420
The disease then moves on,
by the fifth day of the rash,

31:43.420 --> 31:47.210
when fluid begins to accumulate
in pockmarks,

31:47.210 --> 31:51.000
which are then raised and firm
to the touch--

31:51.000 --> 31:55.870
so we'll pass on--now called
vesicles.

31:55.869 --> 31:57.659
They've grown in size.

31:57.660 --> 32:01.730
They've changed in color from
red to bluish or purple.

32:01.730 --> 32:08.040
And they've transformed from
solid to blister-like fluid.

32:08.039 --> 32:10.289
It's umbilicated as well.

32:10.288 --> 32:13.918
The process of what's called
vesiculation,

32:13.924 --> 32:19.334
the rise of this stage of the
rash, takes about three days and

32:19.334 --> 32:21.644
lasts a further three.

32:21.640 --> 32:25.880
It's at this stage that the
physical diagnosis of smallpox

32:25.883 --> 32:29.463
becomes reliable,
with the disease presenting its

32:29.457 --> 32:31.837
most distinctive appearance.

32:31.838 --> 32:35.818
The patient experiences
increasing difficulty in

32:35.821 --> 32:40.851
swallowing and in talking,
due to extensive lesions in the

32:40.851 --> 32:44.751
mucous membranes in the palate
and the throat.

32:44.750 --> 32:51.280
And there's a child at this
stage of the disease.

32:51.279 --> 32:57.649
Then by the sixth day of the
rash, pus begins to form in the

32:57.653 --> 32:58.953
pockmarks.

32:58.950 --> 33:01.830
The patient feels much worse.

33:01.829 --> 33:05.329
Septicemia can set in.

33:05.328 --> 33:08.058
The pustules,
as they're now called,

33:08.063 --> 33:12.283
begin to fill with yellow
fluid, and the lesions become

33:12.280 --> 33:16.510
globular in shape;
a process that takes about two

33:16.509 --> 33:21.109
days, and they're fully matured
on the eighth day of the

33:21.113 --> 33:22.623
eruptive phase.

33:22.618 --> 33:25.508
The patient feels dreadful at
this point.

33:25.509 --> 33:30.369
Fever has risen in proportion
to the severity of the attack.

33:30.368 --> 33:33.428
The eyelids,
lips, nose and tongue are

33:33.433 --> 33:35.343
tremendously swollen.

33:35.338 --> 33:45.518
And we can see a picture of an
adult at that phase of the

33:45.518 --> 33:47.698
infection.

33:47.700 --> 33:51.260
At this point,
the patient is almost totally

33:51.260 --> 33:55.400
unable to swallow or talk,
and deteriorates slowly,

33:55.402 --> 34:00.042
being drowsy most of the time
and restless at night.

34:00.038 --> 34:03.668
Often he or she is in a
condition of delirium,

34:03.673 --> 34:08.143
and thrashes about;
may even try to escape.

34:08.139 --> 34:12.609
The psychological effects
weren't simply a sign of high

34:12.608 --> 34:13.268
fever.

34:13.268 --> 34:16.698
They resulted also from the
involvement of the central

34:16.695 --> 34:21.325
nervous system in the infection,
and the neurological effects

34:21.333 --> 34:26.253
and sequelae could often be
lasting and result in long-term

34:26.251 --> 34:27.441
impairment.

34:27.440 --> 34:30.610
Then, by the ninth day of the
rash,

34:30.610 --> 34:34.830
the pustules were firm and
embedded in the skin,

34:34.829 --> 34:37.769
and for this reason were
likely--and this was important

34:37.773 --> 34:41.523
in the impact of the disease--
to leave permanent scars and

34:41.516 --> 34:45.086
deep pits on the face,
or wherever they appeared on

34:45.085 --> 34:52.215
the body;
if you can imagine by at this

34:52.217 --> 34:53.777
stage.

34:53.780 --> 34:58.950
Another unpleasant aspect at
this stage was that a terrible

34:58.951 --> 35:03.161
sickly smell developed,
the fetor of smallpox,

35:03.163 --> 35:08.413
that physicians claimed that it
was impossible to describe but

35:08.414 --> 35:11.174
was found to be overpowering.

35:11.170 --> 35:15.090
It's now nearly impossible for
the patient to drink,

35:15.094 --> 35:19.174
and even milk caused intense
burning sensations in the

35:19.172 --> 35:20.022
throat.

35:20.018 --> 35:24.388
The patient experiences great
loss in weight--as much as

35:24.389 --> 35:29.159
thirty to forty pounds in an
adult--and may suffer from frank

35:29.157 --> 35:30.347
starvation.

35:30.349 --> 35:32.719
In addition,
there's a complete loss of

35:32.715 --> 35:34.675
muscle tone,
while the face,

35:34.682 --> 35:37.712
in severe cases,
takes on the appearance of a

35:37.713 --> 35:40.873
cadaver,
making the patient almost

35:40.867 --> 35:45.057
unrecognizable,
even to his or her closest

35:45.056 --> 35:46.156
relatives.

35:46.159 --> 35:50.799
The scalp may be one large
lesion, and tangled with hair.

35:50.800 --> 35:53.410
And lesions,
as you can imagine,

35:53.411 --> 35:58.721
under the nails of fingers and
toes were exquisitely painful.

35:58.719 --> 36:02.479
I want to show another
disturbing image--this was

36:02.478 --> 36:07.018
important, but you can look away
if you like--which was the

36:07.019 --> 36:08.899
lesions of the eyes.

36:08.900 --> 36:12.880
Because smallpox was a major
cause of blindness,

36:12.880 --> 36:15.760
as well as death and
disfigurement,

36:15.760 --> 36:17.370
in this period.

36:17.369 --> 36:22.319
Well, after about ten to
fourteen days of rash,

36:22.320 --> 36:26.520
scabs appear,
and these contain live smallpox

36:26.518 --> 36:30.878
virus as well,
and are highly infective and

36:30.876 --> 36:35.856
important in the spread of the
disease by fomites.

36:35.860 --> 36:40.230
At this point,
the fluid portion of the

36:40.226 --> 36:46.316
pustule is absorbed,
leaving behind the solid part.

36:46.320 --> 36:50.240
Large areas of the skin may
begin to peel off,

36:50.244 --> 36:53.824
leaving deeper tissues raw and
exposed.

36:53.820 --> 36:57.240
These areas are all painful,
and contribute to the

36:57.235 --> 37:01.065
frightening appearance and the
misery of the patient.

37:01.070 --> 37:05.420
Fatal cases often occurred from
about the eighth day,

37:05.418 --> 37:10.188
and an important reason was
toxemia, because these lesions

37:10.186 --> 37:13.026
were susceptible to infection.

37:13.030 --> 37:16.450
So, attentive nursing,
good hygiene and sound

37:16.452 --> 37:21.432
nutrition reduced the likelihood
of that sort of complication.

37:21.429 --> 37:24.809
And, to that degree at least,
the prosperous,

37:24.807 --> 37:29.797
the well-nursed and well-cared
for were more likely to survive.

37:29.800 --> 37:33.670
The appearance of the patient
was often described by

37:33.672 --> 37:38.272
physicians as mortification;
the still living patient taking

37:38.269 --> 37:41.189
on the appearance of being
mummified,

37:41.190 --> 37:45.650
and the skin of the face fixed
in a grotesque mask,

37:45.650 --> 37:48.710
with the mouth permanently open.

37:48.710 --> 37:52.840
The appearance of scabs and
crusting though was a favorable

37:52.842 --> 37:56.052
sign in terms of prognosis for
the patient.

37:56.050 --> 37:59.660
But they did lead to one final
torment of the disease,

37:59.655 --> 38:03.255
which was an intolerable
itching that accompanied that

38:03.260 --> 38:06.390
period;
indeed, a large portion of the

38:06.391 --> 38:11.001
scarring that resulted from
smallpox was undoubtedly due to

38:10.998 --> 38:15.128
patients scratching and tearing
at their lesions.

38:15.130 --> 38:18.970
Well, the appearance and
distribution of the pustules was

38:18.971 --> 38:21.511
of major importance for
diagnosis,

38:21.510 --> 38:25.860
and it could be what was called
"discrete smallpox,"

38:25.860 --> 38:31.150
where the rash was--
each lesion was distinct and

38:31.148 --> 38:34.468
separated from the next.

38:34.469 --> 38:39.699
And this meant that you had a
case fatality rate of as low as

38:39.699 --> 38:44.929
about nine percent;
you had a ninety percent chance

38:44.931 --> 38:46.361
of survival.

38:46.360 --> 38:49.250
If instead the lesions were
much closer

38:49.251 --> 38:53.901
together--semi-confluent it was
called--the case fatality rate

38:53.896 --> 38:57.546
rose to something like
thirty-seven percent.

38:57.550 --> 39:02.120
Or in cases of what was called
"confluent smallpox,"

39:02.119 --> 39:06.609
in which the lesions touched
one another and formed a network

39:06.614 --> 39:10.064
surrounded by islands of
unaffected skin,

39:10.059 --> 39:15.079
the case fatality rate was
about sixty-five percent.

39:15.079 --> 39:19.159
So, the appearance of the
lesions was very important in

39:19.155 --> 39:20.435
your prognosis.

39:20.440 --> 39:24.170
The rarest form was hemorrhagic
smallpox,

39:24.170 --> 39:27.100
which had a hundred percent
mortality,

39:27.099 --> 39:30.629
so-called because the natural
clotting mechanisms of the blood

39:30.626 --> 39:33.656
were impaired,
and the victim died of massive

39:33.659 --> 39:35.229
internal hemorrhaging.

39:35.230 --> 39:41.430
Overall, the case fatality rate
for smallpox was estimated to be

39:41.429 --> 39:44.579
about thirty to forty percent.

39:44.579 --> 39:48.709
The virus then attacked not
only the skin and the throat,

39:48.710 --> 39:53.620
but also the lungs,
the heart, the liver and other

39:53.623 --> 39:57.243
internal organs,
and could result in

39:57.235 --> 39:59.385
hemorrhaging and death.

39:59.389 --> 40:03.949
A major danger was also
secondary bacterial infection of

40:03.949 --> 40:07.179
the lesions;
a very common cause of

40:07.182 --> 40:08.222
mortality.

40:08.219 --> 40:12.199
Meanwhile, the lesions of the
mouth and throat were of great

40:12.204 --> 40:17.164
epidemiological importance,
because they're the source of

40:17.159 --> 40:23.219
the viruses that commonly form
droplets in the air and infect

40:23.219 --> 40:24.229
others.

40:24.230 --> 40:27.400
Also, the tongue became swollen
and misshapen.

40:27.400 --> 40:29.080
There was difficulty breathing.

40:29.079 --> 40:33.129
The patient became hoarse,
swallowing was difficult.

40:33.130 --> 40:35.460
And all of that was important.

40:35.460 --> 40:39.470
There were other sources of
anguish and suffering:

40:39.472 --> 40:42.502
blindness, scarring and
disfigurement,

40:42.503 --> 40:44.963
respiratory complications.

40:44.960 --> 40:51.110
But after the drying up of the
rash, the patient began to

40:51.110 --> 40:52.210
recover.

40:52.210 --> 40:55.240
And among the population that
survived,

40:55.239 --> 41:00.209
the symptoms declined and the
patient regained strength and

41:00.213 --> 41:04.933
possessed a lifelong immunity
from a second exposure.

41:04.929 --> 41:08.939
All of this led,
of course, as you can imagine,

41:08.943 --> 41:13.833
to tremendous fear of the
disease--as in this picture--of

41:13.831 --> 41:15.491
Variola.

41:15.489 --> 41:19.319
Well, how did physicians deal
with this disease?

41:19.320 --> 41:23.320
Smallpox no longer occurs
naturally anywhere on the

41:23.320 --> 41:24.040
planet.

41:24.039 --> 41:28.349
But it's worth remembering that
there is still no specific

41:28.346 --> 41:30.836
remedy or cure for the disease.

41:30.840 --> 41:33.760
Treatment, should a case appear
today,

41:33.760 --> 41:37.880
would be largely supportive,
depending above all on

41:37.878 --> 41:41.008
intensive nursing,
to keep the lesions

41:41.005 --> 41:44.855
scrupulously clean,
to prevent bedsores and to

41:44.856 --> 41:48.046
minimize the breakdown of the
skin.

41:48.050 --> 41:51.180
In addition,
modern medicine would replace

41:51.177 --> 41:54.687
lost fluids and nutrients,
and would administer

41:54.686 --> 41:57.406
antibiotics, not to deal with
the virus,

41:57.409 --> 42:00.819
but with the bacterial
infections that are its

42:00.824 --> 42:02.044
complications.

42:02.039 --> 42:04.559
What were traditional remedies?

42:04.559 --> 42:06.949
Some of them were surprising.

42:06.949 --> 42:10.859
One was a great vogue in the
color red.

42:10.860 --> 42:16.060
There was a vogue to hang red
curtains around the bed of a

42:16.057 --> 42:16.967
patient.

42:16.969 --> 42:20.339
Red furniture was brought into
the sickroom,

42:20.335 --> 42:23.695
and patients,
including Queen Elizabeth I of

42:23.702 --> 42:26.992
England, were wrapped in red
blankets.

42:26.989 --> 42:31.509
Later on, the discovery of
ultraviolet rays in fact gave

42:31.505 --> 42:35.195
new impetus to this traditional
mania for red,

42:35.201 --> 42:38.241
and red glass went up on
windows.

42:38.239 --> 42:41.889
In the late nineteenth century,
medical journals published

42:41.887 --> 42:45.857
studies suggesting also that red
light could be soothing to the

42:45.856 --> 42:49.556
eyes of the sufferer,
and that perhaps it prevented

42:49.561 --> 42:51.111
scarring of the skin.

42:51.110 --> 42:53.210
So, that was one factor.

42:53.210 --> 42:57.320
Another idea that was very
common was to open the pustule

42:57.318 --> 43:00.618
with a golden needle,
to drain the fluid,

43:00.619 --> 43:05.649
and then sometimes the lesions
were cauterized in an attempt to

43:05.648 --> 43:08.988
prevent scarring;
procedures that were

43:08.987 --> 43:10.787
exceedingly painful.

43:10.789 --> 43:13.639
The next idea was what was
called "the hot

43:13.641 --> 43:16.061
regimen,"
to pile the sufferer with

43:16.061 --> 43:18.921
blankets,
to induce him or her to sweat

43:18.923 --> 43:21.743
profusely,
to rid the body of the

43:21.739 --> 43:23.639
over-abundant humor.

43:23.639 --> 43:27.509
Or the patient could be
immersed in a hot bath.

43:27.510 --> 43:31.050
Light and fresh air,
according to this therapeutic

43:31.045 --> 43:33.295
fashion,
were deemed to be harmful,

43:33.295 --> 43:35.475
and the patient was kept in the
dark,

43:35.480 --> 43:38.780
if possible,
with minimal ventilation.

43:38.780 --> 43:42.940
Sunlight was said to aggravate
the disease and increase

43:42.942 --> 43:43.792
scarring.

43:43.789 --> 43:48.799
And sometimes patients were
given internal medications,

43:48.800 --> 43:54.090
sudorifics, to help the
evacuation of the excess humor.

43:54.090 --> 43:57.370
The opposite was also tried,
the so-called "cold

43:57.373 --> 43:59.903
regimen,"
to keep the room cool,

43:59.900 --> 44:03.340
and frequently to sponge down
the patient with cold water,

44:03.340 --> 44:06.430
to place-ice bags on the face.

44:06.429 --> 44:12.669
Then there was purging and
bloodletting.

44:12.670 --> 44:15.710
There was also the
administration of opiates,

44:15.711 --> 44:19.171
in the nineteenth century,
and especially morphine,

44:19.170 --> 44:21.660
to calm the patient in
delirium.

44:21.659 --> 44:25.389
Astringent eye drops were
resorted to.

44:25.389 --> 44:30.399
A particularly perverse theory,
with no empirical basis,

44:30.400 --> 44:34.870
was the idea that scarring on
the face could be reduced or

44:34.869 --> 44:39.179
prevented by causing more
intense irritation of the skin

44:39.181 --> 44:42.421
elsewhere;
so that mustard plasters,

44:42.416 --> 44:46.426
mercury and corrosives were
applied on the back,

44:46.431 --> 44:48.911
in order to save the face.

44:48.909 --> 44:52.789
There were also all kinds of
local applications to the face,

44:52.791 --> 44:54.701
to try to prevent scarring.

44:54.699 --> 44:57.999
Nitrate of silver,
mercury, iodine,

44:58.003 --> 45:03.753
mild acids, a lotion of sulfur;
all of those had their vogues.

45:03.750 --> 45:07.680
There were ointments and
compresses of virtually every

45:07.684 --> 45:09.544
substance known to man.

45:09.539 --> 45:13.449
Some physicians held the theory
that their preparations would

45:13.445 --> 45:16.175
soften the lesion and mitigate
scarring.

45:16.179 --> 45:19.559
So, indeed, ingenious doctors
applied lint,

45:19.557 --> 45:23.817
boric acid or glycerin;
or they covered the face with a

45:23.820 --> 45:27.450
mask, leaving holes for the
eyes, nose and mouth.

45:27.449 --> 45:31.709
Or they wrapped the face and
hands in oiled silk.

45:31.710 --> 45:35.960
Alcoholic beverages were
administered to deteriorating

45:35.956 --> 45:38.676
patients to revive their energy.

45:38.679 --> 45:43.609
And sometimes delirious
patients were actually tied to

45:43.610 --> 45:44.820
their beds.

45:44.820 --> 45:49.230
Some doctors recommended
restraints, such as splints,

45:49.226 --> 45:52.606
in later stages,
to prevent patients from

45:52.614 --> 45:55.924
scarring their faces by
scratching.

45:55.920 --> 45:59.130
After hearing of all of these
treatments for smallpox,

45:59.130 --> 46:02.530
perhaps you'll appreciate the
work of Thomas Sydenham,

46:02.530 --> 46:07.510
in the seventeenth century,
the so-called English

46:07.512 --> 46:11.342
Hippocrates,
who decided that the wealthy

46:11.340 --> 46:16.130
and noble who received extensive
attention and treatment for

46:16.126 --> 46:21.556
smallpox perished of the disease
more frequently than the poor,

46:21.559 --> 46:24.249
who had no access to treatment.

46:24.250 --> 46:28.400
And his advice was that the
best physician was the one who

46:28.396 --> 46:29.556
did the least.

46:29.559 --> 46:33.209
He was an advocate of
therapeutic minimalism.

46:33.210 --> 46:37.190
He advised instead a simple
cool regimen,

46:37.193 --> 46:42.773
giving his patients fresh air
and light bed coverings.

46:42.768 --> 46:47.458
Well, that's how the disease
afflicted the human body.

46:47.460 --> 46:51.220
What I want to do next time,
now that we understand this

46:51.224 --> 46:54.514
terrible disease and the
suffering it caused,

46:54.510 --> 46:57.700
is to deal with its impact
historically,

46:57.699 --> 47:01.609
its effect on society,
and to look at the development

47:01.608 --> 47:06.598
of a public health strategy,
which was to be vaccination.

47:06.599 --> 47:11.999