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So, let me move on now to smallpox.

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As you'll see
as I go through the rest of this talk,

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I happen to have a profound interest

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in infectious diseases because that's my area
of clinically and immunology.

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So, let's talk a little bit about smallpox,
which has a pretty neat history.

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Smallpox was first described by Al-Rhazi,
who I had mentioned earlier,

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probably about 900 AD.

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In the 11th century,
there actually were protective measures

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being used throughout the world,
taking scabs from smallpox pustules

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and putting them in the nostrils
of a healthy subject.

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And that actually offered some protection
if you didn't get smallpox.

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People were wearing the clothing
of someone who had the disease.

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People ingested
powdered fleas from infected cows,

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which may have perceived
the relationship of cowpox to smallpox.

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In the 1720s,

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the process of what's called variolation
was practiced in Africa, China, and India,

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where you would take a scab from a patient
who had smallpox, remove it from the subject,

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and take the contents of that scab
and scratch it into a healthy person.

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Most people got protected;
some people got smallpox.

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And Lady Mary Worley Montague,
who was British and the wife of the British

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ambassador, observed, in Turkey,
in Constantinople, this variolation process.

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And she brought it to London
and she even inoculated her own two children.

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And a hospital for smallpox
inoculation was founded

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in London in 1745 using this approach.

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The first known use of cowpox
to protection against

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smallpox was done
by Benjamin Jesty, who lived in 1736 to 1816.

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And he was a farmer who lived in a village

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of Yetminster
in North Dorset, United Kingdom.

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And he was convinced that milkmaids
who contracted cowpox

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were protected from smallpox.

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And in 1774,
he inoculated himself, his wife, and two sons

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with cowpox lymph
from the underside of a cow udder.

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And in1805,

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he publicly inoculated his son, Robert,
with live smallpox after he had inoculated

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or immunized him, and he demonstrated
that his son was protected.

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So, this was before Jenner.

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But what Jenner did in
1776 was actually do a large study.

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And here you see him
vaccinating James Phillips,

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the first person who was vaccinated.

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And he did a large study, and he recorded
the data, and talked about it.

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And it was after Jenner's work with smallpox

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that a vaccine that was efficacious
was developed.

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Now, before we conclude smallpox,
I just want to mention one historical fact.

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I don't want to dwell on Lord
Jeffrey Amherst.

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He actually did the first biological warfare
of taking blankets from people

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who were infected with smallpox and giving it
to the Indians in the French Indian War.

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That's pretty horrible.

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But George Washington
did something remarkably clever.

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In 1775 and 1776,
when the British were surrounding Boston

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and the Continental Army in the United States
was threatened,

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the British Army had an epidemic of smallpox,
which had not hit the Continental Army.

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And Washington
made the decision that he wanted

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to do
the variolation technique in the soldiers.

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But he wouldn't do it without the consent
of the Continental Congress.

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And so, he got John Adams, who,
on July 3, 1776, the day

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before the Declaration of Independence
was signed, he got Adams to get

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the Continental Congress to give approval for
mass immunization of the Continental Army.

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And this was, to my knowledge,
the first example of mass

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immunization of -- in the military
or probably anywhere else.

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And it worked.

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It probably saved the Army and enabled
the United States to beat

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-- or the Continental Army
to beat the British, eventually.

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And, now, of course,

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smallpox has been eradicated
through the work of D.A.

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Henderson.

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And the last case was in 1977,
and the World Health

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Organization declared smallpox
completely eradicated in 1980.

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So, genetics.

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We all know about genetics.

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We know about Mendel, who was the Father
of Genetics, working with plants.

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And you may not know about Barbara
McClintock, who lived from 1902 to 1992,

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and was a fabulous cytogeneticist,
and did groundbreaking research

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in developing the technique
of visualizing maize of corn chromosomes,

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and used microscope analysis
to generate many fundamental ideas,

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and discovered transposition
and used it to demonstrate the genes

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that are responsible for turning
physical characteristics on and off.

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And in 1983, she won the Nobel Prize for her
discoveries of mobile genetic elements.

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And you know about Darwin, who lived
-- and in 1859, published his book, "On

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the Origin of The Species."
You may not know that he created

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the first tissue bank and demonstrated
the importance of meticulous records.

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During his travels, he took tissues
from all the different species

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that he studied,
and he actually created a tissue bank.

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So, clinical medicine
depends on epidemiology for much of the work.

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And I want to just mention
John Snow, who was an anesthesiologist

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who lived from 1813 to 1858, who was British.

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And he was a real medical hygiene
pioneer and,

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really,
the father of modern epidemiology for work

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tracing the course of a cholera
epidemic in Soho, England, in 1854.

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And he created this spot
map in the city of London in Soho

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to illustrate each case of cholera
during this epidemic.

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And he demonstrated
that it all centered around a water pump.

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And he illustrated the connection
between the quality of water source

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and the cholera cases.

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And he said, "Remove the water pump and
you'll get rid of the cholera." And they did.

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And then, the community went ballistic
because they had to walk

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long distances to get the water,
so they reopened it.

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The cholera came back.

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So, he really proved his point.

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Then they closed the pump
and the epidemic subsided.

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So, this was a major event
in public health history.

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Maybe the greatest public health
invention in the 1800s

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was by Semmelweis,
who I'll tell you about in a minute.

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But remember what I told you,
that Sushruta had advocated

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sterilization of wounds and Hippocrates
promoted clean hands for wound management.

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But it was this man, Ignaz Semmelweis,

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who really solidified
the importance of sanitation in medicine.

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And he lived from 1848 to 1863, a short life.

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He studied puerperal sepsis
in Vienna, over the protests of his chief.

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He was an anesthesiologist.

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He had noted that the sepsis rate
was three times higher in Division

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One in his hospital than in Division Two.

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And these two divisions were identical

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except medical students worked in Division
One and midwives in Division Two.

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And he had a dear friend who died following
infection of an autopsy that his friend did.

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He was a pathologist.

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And it was autopsy in a patient
who had a wound similar to puerperal sepsis.

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And this led him to the primary hypothesis
that the infection that was seen in the women

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who were delivering
babies came from the autopsy room

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by the medical students
to these women who were giving birth.

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So, he said students had to wash their hands
and he used chlorinated lime solution.

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This basin still exists that he used.

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And when he did that,
the mortality rate dropped from 18 percent

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to 1 percent per year
and, in some months in 1848, it was zero.

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And these are the data that he published.

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And you can see by this yellow line,
which is the number of women who had sepsis

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who died, and the red arrow is
when he started having them wash their hands,

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and it immediately plummeted.

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So, he told his chief about this,

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and the chief didn't believe his data,
and he was fired.

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So, then he moved to Budapest, Hungary,
where he repeated these experiments

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and got the same results.

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And wrote a paper,

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The Etiology, Understanding,
and Prevention of Puerperal Sepsis,

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and it was rejected by the Vienna
Medical Journal.

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And, ultimately, he had to pay to get
this work published, but it was published.

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And I can tell you, he had a sad outcome.

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He went crazy because nobody believed him.

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And he was admitted to a mental hospital,
and he cut his leg

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on the edge of a bed,
and he died of puerperal sepsis.

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Now, his work was known
by some folks in the United States

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and I'll tell you about that in a second.

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But in the interim, in 1882, Joseph Lister

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also was working on the importance of sepsis
in the operating room,

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and he used carbolic
sprays to clean wounds, open wounds.

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And he showed that this would reduce
infection.

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So, the person who advocated for Semmelweis
was Oliver Wendell Holmes,

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Sr., the father of the great Supreme Court
justice in the United States,

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who was an obstetrician
who worked at Massachusetts General Hospital.

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And he didn't repeat Semmelweis's
experiments, but he believed them.

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And he went around and spoke this up
and certainly got clean hands

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and washing hands as an integral part
of the public health of hospitals.

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Sadly, it's still a huge problem.

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And I can you, in this hospital,
at the NIH Clinical Center, a few years ago,

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we had an epidemic of a multi-drug resistant
klebsiella infection.

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And it was clearly linked

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to people not washing their hands
in an aggressive enough fashion.

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So, something as simple as washing hands
is phenomenally important.

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So, let me tell you a little more
about surgery, more modern surgery.

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I can't escape telling you about John Hunter,

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who lived from 1728 to 1793,
who really changed the nature of surgery.

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He was a Scottish anatomist and a surgeon.

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His older brother was an established surgeon.

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And his mother
didn't know what to do with him,

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so she sent him to work with his brother.

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And his brother, who was a surgeon,
told him to go out and rob graves.

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And he became --

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they would take these corpses and teach
anatomy to people who were interested.

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And he became quite the skilled
anatomist and, then, surgeon.

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And one of the things he did
is determine the nature of venereal disease.

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And he actually inoculated himself

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with the infected material
from someone who had syphilis.

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And he got syphilis and he eventually
had heart damage from the syphilis.

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There's a great book called, "The Knife Man."
And if you're interested,

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I suggest you read it.

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It's a very colorful book about his life.

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Anesthesia,

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we can't mention without mentioning
William T.G.

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Morton, who was a dentist
who lived from 1890 [sic] to 1868.

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And he demonstrated that ether,
which he called letheon, worked.

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And he did a demonstration in 1846, October

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16, 1846, at Mass General Hospital in Boston,
demonstrating that surgery

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could be conducted on a person
while they're asleep with no pain.