Magic Bullets and The Super Organisms
Fall 2009
Popularizing Microbes
People generally dont like
Microbes.
They assume that all microbes
are Bad.
So, Microbiologists have become
like buffalo hunters, but instead of buffaloes, they seek Magic
Bullets.
Louis Pasteur
got the ball rolling when he said that microbes
are a menace.
Leeuwenhoek and Bacteria
About 300 years ago he
discovered Bacteria.
He also concluded that life
lives on life -- it is cruel, but it is Gods will.
But Bacteria are all around us.
One gram of soil contains
perhaps 1 to 10 billion bacterial cells.
How do they reproduce?
Bacteria and Viruses
Bacteria are not
viruses and viruses are not bacteria.
Viruses are the
living dead or bad news wrapped in a protein.
They are floating
bits of genetic material.
They can be either
DNA or RNA strands.
They proceed then
to hijack a cell, like Tony Soprano would hijack a truck of Pokemon Cards.
Rats, Rats, and More Rats
Rats still remain a vector.
Or a carrier of disease.
What do we know about rats?
First of all the Black Rat (Rattus
Rattus) was replaced by the Brown Rat (Rattus Norvegicus), which did
not come from Norway.
But swarmed from Russia and
Central Asia and replaced the Black Rat
even in North America.
What Do We Know About Rats?
The Problem with Rats
Rats are sometimes called germ
elevators because they help spread disease.
Including:
Plague.
Cholera.
Typhus.
Leptospirosis, a disease that is
caused by bacteria spread by rat urine contaminating water or food.
The Search for the Cause of the Plague
Alexandre Yersin studied at the
Pasteur Institute and went in search of the cause of the plague.
He did this independently of all
other efforts in 1894.
But so did a Japanese scientist,
Shibasaburo Kitasato who published his findings too in English.
And managed to develop a serum
to be used in its treatment.
As the Plague occurred since?
Yes
it also broke out in San
Francisco too in 1900-1909.
Cholera
Cholera is the illness caused by
a bacterium called Vibria cholerae. It infects people's intestines,
causing diarrhea, vomiting and leg cramps.
The most common cause of cholera
is by someone eating food or drinking water that has been contaminated with the
bacteria.
The diarrhea and vomiting
brought on by the infection quickly leaves the body without enough fluid.
The following dehydration and
shock can kill a person within hours.
Types of Typhus
Epidemic louse-borne
typhus is caused by
Rickettsia prowazekii
and infection is favored by crowded, unsanitary living conditions such as in
concentration or the more primitive refugee camps - especially those in cold
areas. Epidemic louse-borne typhus is currently most prevalent in mountainous
areas of Africa, Asia, and Latin America.
Scrub typhus
is transmitted by the bite of mites or chiggers infected with
Orientia tsutsugamushi
(of the family Rickettsiaceae) and is found in most areas of Asia.
Endemic (murine)
typhus is transmitted by the bite of fleas
infected with Rickettsia typhi. Endemic
typhus is found worldwide.
What is Typhus
Typhus fever, also called
typhus, is a disease that occurs throughout the world in areas where people and
rats occupy the same buildings and where large numbers of mice live.
It is also called murine typhus
fever and is rare in the U.S.
Who gets typhus?
Anyone can get
typhus but it occurs more often in people
whose occupations or living conditions bring them into contact with rats.
How is the disease spread?
It is not
directly spread from person to person.
People get typhus after infective rat fleas contaminate fresh skin wounds or the
flea bite site.
Malaria Regions of the World
The Problem of Malaria: A Case
Study
It was very difficult to
determine where Malaria came from.
Wherever it came from it spread
very quickly.
From Sweden to South America, no
place was spared.
In 1870, Pasteur and later Koch
established the revolutionary principle of specific microbes and specific
diseases.
By 1880 a French physician in
Algeria discovered the parasite that caused Malaria.
Major Charles-Louis-Alphonse
Laveran saw the Plasodium falciparum.
Life Cycle of the Malarial
Parasite
The Coming of Ronald Ross
Ross was the man
most unlikely to succeed.
He was totally
ignorant of mosquitoes and could not tell one of a mosquito from the other.
He was not trained
in Zoology and considered himself a poet-playwright of sorts.
His father had
other ideas.
If Ross was not
going to be a soldier, then he would be a doctor.
He was sent to
India and feel in LOVE with Rosa
Bessie Bloxam,
who, like Mrs. Taylor had considerable impact on him.
Ross set out to
find the vector that caused malaria.
What Did Ross Find?
Species of the Malaria
Parasite
Plasmodium falciparum.
Plasmodium vivax.
Plasmodium ovale.
Plasmodium malariae.
Cures for Malaria
Proper
Sanitation.
Quinine.
Chloroquine.
Atebrin
DDT.
Malaria Vaccines.
Where Did It Come From?
May have come to Europe from
N.E. Africa about the time of the birth of Christ.
The Huns probably spread the
virus too in the 450s.
After that, no one was safe.
Types of Smallpox
Variola Major, Minor,
Intermedius
A Horrifying Killer
The dreaded killer would swept
through Asia, Africa, Europe, and the New World.
Lethality of Smallpox
It killed one out of every four
victims.
At first the victim would not
know what had happened.
Symptoms of Smallpox
By the ninth day of the
infection, the first symptoms appear.
They include headache, fever,
chills, nausea, and backaches.
Delirium can occur and last for
up to three or four days.
Those with a fair complexion
will develop a rash with greater intensity around the face and upper torso.
Over time the red spots become
pustules.
The Coming of Death
Many died during the first few
days of the infection.
Once infected there was no
cure.
Often people died from secondary
infections.
No one was spared the horrors of
this disease.
Those Fortunate to Live
Those that survived were
disfigured for life.
Many would be blinded.
Early Treatments
Bleeding
The Red Treatment
Inoculation and Vaccination
In 1762 Robert Sutton and his
six sons introduced inoculation.
This came from the East and was
used in China.
The real hero was Edward Jenner
(1749-1823).
He inoculated his son and his
nurse with Swine Pox. Then later with Smallpox in 1790.
With no reaction.
Then he switched to Cowpox as a
medium for his Vaccination.
Jenner at Work
Some other Info About Smallpox
The
Variola
virus belongs to a genus of
Orthopoxviruses or true pox viruses.
Others in this group include
buffalopox, camelpox, monkeypox, mousepox, rabbitpox, and raccoonpox.
Sometimes these monikers are
misnomers since cowpox and monkeypox are actually carried by rodents that infect
monkeys and cows.
Lady Mary Wortley Montagu
She was a London socialite and a
wife member of Parliament.
She was a famous beauty in her
youth.
Then she contracted Smallpox at
the age of 26.
This happened after her brother
became ill with the disease.
Lady Montagu and Smallpox
She survived but was severely
scared.
She lost her eyebrows.
In 1717 accompanied her husband
to Constantinople.
Shortly after her arrival she
became familiar with variolation.
She had her five year old son
inoculated this way.
Variolation
There were different forms of
the procedure.
The Chinese used a form called
insufflation.
In Russia, they slapped their
skins with the stuff.
In 1721, Lady Montagu brought
the procedure to England and arranged for the Princess of Wales to sponsor a
public demonstration.
Six prisoners who were sentenced
to be hanged were variolated and then exposed to active smallpox.
They were never infected.
Lady Montagu and Smallpox
She survived but was severely
scared.
She lost her eyebrows.
In 1717 accompanied her husband
to Constantinople.
Shortly after her arrival she
became familiar with variolation.
She had her five year old son
inoculated this way.
Louis Pasteur (1822-95) and
All the Rest
Joseph Lister followed in the
wake of Pasteurs discovery of microorganisms in 1957.
Lister introduced antiseptic
surgery in the 1860s.
Louis Pasteur (1822-95)
The Germ Theory of Disease
Pasteur was the father of the
germ theory of disease.
He discovered that
microorganisms were responsible for the spoiling of milk.
He spent his life cultivating
organisms that cause disease.
In 1879 he had a piece of luck
to discover that chickens that were vaccinated with a weakened strain of Chicken
Cholera that protected them against the disease.
The process that he discovered
was called Attenuation.
Attenuation became the basis for
the development of several vaccines.
Robert Koch ( 1843-1910) and
His Four Postulates
A Specific organism must be
associated with a specific illness.
The organism must be isolated in
pure culture and then subculture over repeated generations.
When inoculated into healthy
susceptible animals and the organism once again must cause the disease.
The organism must be isolated in
pure culture form the samples taken from the sick animal.
Robert Koch Wins the Noble Prize
in Medicine in 1905
Kochs Greatest Achievement
His greatest achievement came
with the discovery of the microorganism that caused tuberculosis.
This was mycobacterium
tuberculosis.
Which shared the same genus with
the mycobacterium that caused leprosy.
This was especially important
since tuberculosis killed one out of every seven victims.
Paul Erlich
He was one of Kochs able
assistants.
He came up with the concept of
the minimal lethal dose.
He developed dyes that allowed
microbiologists to see microorganisms.
He also believe that body may
harbor what he called magic bullets.
Then in 1906 the Prussian
scientist discovered treponema pallidum, the agent that caused syphilis.
Erlich than found a cure, first
Salvarsan, but it proved too dangerous and it was replaced with Neosalvarsan.
This was the most effective cure
until Alexander Flemings discovery of penicillin in 1928.
Background of the Disease
The disease has been around for
a long time.
During the Middle Ages, Kings
administered the Kings Touch to those who had Scrofula.
Tuberculosis came in many
different forms from Consumption to Lupis Vulgaris.
The most common type was
Consumption, better known as TB.
Early Treatments
Before Robert Koch discovered
the bacillus that caused TB in 1882 there was only one treatment.
That treatment was pioneered by
George Bodington.
This was called the
Sanatorium Method.
It involved open air, rest, and
recuperation as a means of making the disease go into remission.
By 1930, 90,000 people died of
TB in the U.S. and 50,000 in Great Britain, and 66,000 in France.
Victory
over
TB
A number of key people played a
role in the defeat of the White Plague.
One was
Selman Waksman
a microbiologist at Rutgers University, who believed that antibiotics could
defeat the disease.
Another was
Gerhard Damagk
a microbiologist who worked for Bayer and developed
Protosil
and later the thiosemicarbazones.
The last pioneer was a
Jurgen Lehmann,
who discovered Para-aminosalicylic Acid (PAS).
All of these men played a key
role in the defeat of TB.
Streptomycin
The wonder drug was discovered
by Waksman, but more importantly, by his graduate student,
Albert Shatz.
Later on, when Waksman won the
Nobel Prize, Shatz demanded a part of the award.
At first Streptomycin was
effective, but over time, the bacillus developed a resistance and required
multiple drugs.
By the 1970s TB was on the
decline and public health officials thought the war was won.
How wrong they were.
Then along came AIDS.
Introduction to Polio
Parents feared this disease like
no other.
It made its first appearance in
1835.
For the most part, the victims
were children.
Like Smallpox, it did not
respect rank or privilege.
The disease is spread by fecal
matter.
But it took time to discover
that fact.
The agent is a virus and enters
the body orally.
The 1916 Epidemic of Polio
Twenty states experienced a
major outbreak.
That is if they had reporting
laws.
All told 27,363 cases of polio
were reported.
New York had the most with 9,023
of which 2,448 died.
The publics reaction was to
flee the cities during the summer.
American Perceptions Changed
Defeating Polio
First thing you had to do was
discover the cause.
Which was done in 1908 by the
Austrian Karl Landsteiner.
Who discovered that it was
virus.
Later he would win the Nobel
Prize in Medicine for his discovery of different blood types A, B, AB, and O.
But the discovery that it was a
virus was the first step.
The Development of the Modern Charity
Initially the most successful
organization was the National Tuberculosis Association that came up with the
Christmas Seals in 1907.
Roosevelt had to come up with
the similar program.
But now it had to happen during
the Depression.
The key was the Presidents
Birthday Balls in 1934.
But the real achievement came
with Eddie Cantor.
The Defeat of Polio
The fight against Polio really
started in 1938
when FDRs law partner, Basil
OConnor, organized the
National Foundation for Infantile Paralysis.
Eddie Cantor
gave it a unique way to raise money and as a result it was called
The March of Dimes.
Money flocked in an rose from
1.83 million in 1938 to 67 million by 1955.
Money was spent on research and
to fund Warm Springs.
Role of Basil OConnor
The March of Dimes brought in
tons of money.
That OConnor wisely used by
establishing National Foundation for Infantile Paralysis.
He hired Thomas Rivers as a
medical advisor.
Then funneled funds to research
institutions.
This was significant after what
had happened earlier.
The Initial Failures
William H. Park, a professor of
bacteriology at NYU Medical School.
Recommended Maurice Brodie in
1934.
Who decided to use a
killed-virus vaccine.
But the trials were fraudulent.
And Park and Brodie failed.
But worse was to come.
The Case of John A. Kolmer
He was working on a live-virus
vaccine in Philadelphia.
He started in 1934.
He thought he was ready.
And then used a monkey medium.
Vaccinated himself and his two
sons and then 29 other children.
Problem was the vaccine was not
fully cooked.
Result was a major tragedy when
he gave his vaccine to 10,000 children.
Nine children came down with the
Mahoney Strain of Polio and died.
Jonas Salk
A MD, expert in Virology, at the
University of Pittsburgh.
His research proved promising
and OConnor funded his research.
Salk advocated the killed virus
vaccine.
The
AMA did not agree and supported
Albert Sabin.
Who advocated a live virus
vaccine.
Because of Salk
There were no more Iron Lungs.
Parents no longer had to fear
the summer.
Young bodies of children were no
longer deformed.
But today, more people remember
Albert Sabin.
Yet it is the Fiftieth
Anniversary of the defeat of Polio with the help of the
Salk Vaccine
Typhoid Fever
Typhoid fever is contracted by
people who eat or drink water that has been infected with
salmonella typhi.
The symptoms include high fever,
severe headache, nausea, and loss of appetite.
It is sometimes accompanied by a
severe cough and/or diarrhea.
Fatality rates had reached 10%.
There has been 17 million cases
annually with 600,000 deaths.
It killed 6,000 between
1607-1624 in Jamestown.
In 1880, Karl Erberth identified
the bacteria that causes typhoid.
The Strange Events in Oyster Bay in August
1906
This was the area for rich and
wealthy New Yorkers to summer.
It was the home to T.R.
Then the family of Charles Henry
Warren came down with Typhoid.
Especially the second daughter,
two maids, the gardener.
Everything was checked out.
Then the cook disappeared.
The Case of Mary Mallon
The owner of the Warren summer
home summoned Dr. George Soper to investigate.
With Mary Mallons disappearance
was very suspicious.
He tracked down her previous
employment history and discovered that others experienced the same situation.
Then he heard that a family was
struck by typhoid on Park Avenue.
The Detention of Mary, aka Typhoid Mary,
Mallon
All told she infected 53 people
of which five died.
She was detained for three years
and had to promise that she would never serve food again.
But she broke her word.
Five years later she had
infected an additional 25 people.
In 1915 she was sent to North
Brother Island and spent the last 23 years of her life.
What Happened to Mary Mallon?
Robert Koch discovered that
Typhoid can stay active in people that appear not to be ill with the disease.
That is after they were sick.
However, they never fully
recovered.
Instead the bacteria is lodged
in the gall bladder and is passed through the victims urine and feces.
Mary Mallon was the first
documented carrier in the US.
The Spanish Lady
We do know that it spread very
rapidly.
It caused death at a very early
age, often from secondary infections.
No one, no where was spared from
this disease.
Something had to be done to keep
the public from panic.
Face masks were introduced and
public events were called off.
All told, approximately 20 to 40
million people worldwide had died.
More Americans died of the
Spanish Flu (675,000) than died in all American wars in the twentieth century.
The Spanish Flu in World War I
The flu was especially deadly
for those between 20 and 40.
About 43,000 American Doughboys
died of the new strain.
The Flu may have started at Camp
Funston, in Kansas of all places.
Americans responded by canceling
all activities.
About 200,000 died in October
alone.
They didnt know what caused the
disease.
The Coming of HIV
HIV is old, somewhere between
10,000 or 100,000 years.
The disease is also common
monkeys too and is called SIV and is related to HIV-1 and HIV-2 strains.
AIDs probably infected people
earlier than many people thought.
The Story as We Know It
One of the first victims was Dr.
Grethe Rask who died on Dec. 12, 1977.
She died of Pneumocystis Carinii
Pneumonia (PCP).
By early 1981, there was
something happening in America.
Especially among the homosexual
community when homosexual males were dying of all sorts of illness: PCP,
Karposis Sarcoma (KS), Yeast infections, and other illnesses.
The Role of the CDC
The CDC started a cluster study.
They thought they found their
man, since of the first 248 men diagnosed with GRID (an earlier name for AIDS),
40 had sex with him.
Especially in outbreaks in New
York and LA.
CDC realized that they had a
Holocaust in the making.
Particularly for hemophiliacs
and they questioned the safety of the nations blood banks.
Then came the link between AIDS
and TB.