Unraveling the Mystery of Immunity | Dr. James Crowe, Jr. | TEDxNashville
Summary
TLDRThe speaker, a physician and scientist, recounts a profound experience with the death of a child in East Africa, igniting a passion to combat infectious diseases. He discusses the human immune system's complexity, highlighting its vast potential to create antibodies, and the importance of vaccination as evidenced by smallpox eradication. The talk also explores modern challenges, like the 1918 flu, and innovative approaches in synthetic genomics to harness natural antibodies from survivors as potential treatments for future outbreaks.
Takeaways
- 🌱 The speaker is a physician and scientist with a focus on the human immune system, motivated by a profound experience in East Africa witnessing the impact of infectious diseases on children.
- 💔 A pivotal moment in the speaker's career was when they had to return a deceased child to its mother, an event that instilled a lifelong commitment to combating infectious diseases.
- 📚 Historically, pandemics like the Black Death, the 1918 influenza, and smallpox have had devastating effects on human populations, with death tolls reaching into the millions.
- 🌟 The eradication of smallpox through vaccination represents a significant victory for humanity against infectious diseases, demonstrating the power of medical science.
- 🛡️ The human immune system is a complex defense mechanism that circulates throughout the body, with white blood cells playing a crucial role in fighting infections.
- 🧬 The Human Genome Project revealed that humans have approximately 25,000 genes, a number that initially seemed insufficient to account for the diversity needed to combat pathogens.
- 🔬 The immune system's ability to generate a vast array of antibodies through gene combinations and mutations provides a deep and rich defense against a multitude of pathogens.
- 🧬🌌 The potential diversity of antibodies in the human body is estimated to be greater than the number of stars in the galaxy, highlighting the immense capacity of the immune system.
- 🧪 Modern techniques in synthetic genomics and sequencing allow scientists to study and replicate antibodies from individuals who have survived infections, offering new therapeutic possibilities.
- 🌐 The speaker's team is undertaking an ambitious project to sequence all antibodies in the human population, which could lead to a publicly accessible database for scientific research.
- 🛡️🌟 The human immune system is a marvel of nature, capable of incredible feats of defense and adaptation, and each person carries this 'universe within' them.
Q & A
What was the speaker's profession and area of study?
-The speaker is a physician and a scientist who studies the human immune system.
Where did the speaker work during his senior medical student years?
-The speaker worked in a rural hospital in East Africa, among the Kip, Cigy people.
What was the challenging aspect of the speaker's experience in East Africa?
-The challenging aspect was the overwhelming burden of infectious diseases in young children.
What event during the speaker's time in the hospital deeply affected him?
-The event was when the speaker encountered a child who had no heartbeat and had to inform the parents of the child's death.
What did the speaker vow to do after the traumatic experience with the child's death?
-The speaker vowed to dedicate his life and career to combating infectious diseases, especially for the most vulnerable.
What historical pandemics were mentioned in the script?
-The script mentioned the Black Plague, the 1918 influenza pandemic, and smallpox.
How did humanity achieve the eradication of smallpox?
-Humanity achieved the eradication of smallpox through vaccination using a weakened virus.
What is the significance of the immune system in the human body?
-The immune system is the body's defense mechanism that wards off or cures infections.
How does the speaker describe the diversity of antibodies in the human immune system?
-The speaker describes the diversity of antibodies as having combinatorial diversity, with the potential to create 10 to the 18th different antibodies.
What is the process of synthetic genomics mentioned in the script?
-Synthetic genomics is the process of creating artificial DNA sequences, which can be used to produce specific antibodies in a lab setting.
How did the speaker's team obtain antibodies from a survivor of the 1918 pandemic?
-They obtained blood from 100-year-old subjects who had experienced the 1918 infection and extracted antibodies from their blood that could kill the virus.
What is the potential application of the antibodies obtained from Michelle Barnes, a survivor of Marburg virus infection?
-The antibodies obtained from Michelle Barnes are being developed as a therapy for future cases of Marburg virus or in the event of an outbreak.
What does the speaker suggest about the human immune system's capability against infectious diseases?
-The speaker suggests that the human immune system is a deeply complex and powerful system capable of combating a vast array of infectious diseases.
Outlines
😔 Heartbreaking Encounter with Childhood Mortality
The speaker, a physician and scientist, recounts a profound experience from his time as a senior medical student in a rural East African hospital. Overwhelmed by the prevalence of infectious diseases, he faced a particularly challenging moment when he was unable to save a child's life. This encounter deeply affected him, leading to a personal vow to dedicate his career to combating infectious diseases, especially for the most vulnerable. The narrative emphasizes the historical impact of pandemics, such as the Black Plague and the 1918 influenza pandemic, and the speaker's commitment to the field of immunology.
🛡️ Triumphs and Challenges of the Immune System
This paragraph delves into the speaker's professional journey and the broader context of infectious diseases. It highlights the success of vaccination in eradicating smallpox, a historic achievement marked by the WHO's declaration in 1980. However, the speaker also underscores the ongoing challenges, such as recent pandemics and outbreaks like bird flu, SARS, and Ebola, emphasizing the need for constant vigilance and innovation in the face of evolving pathogens. The paragraph concludes with a reflection on human vulnerability and resilience, and a call to consider the role of the immune system in personal and public health.
🔬 Exploring the Complexity of the Immune System
The speaker provides an in-depth look at the human immune system, starting with a demonstration of blood cell observation under a microscope. He discusses the role of white blood cells in immunity and then transitions into the genetic basis of the immune system. The Human Genome Project is mentioned, revealing the relatively small number of genes in the human body. However, the speaker explains the combinatorial diversity of antibodies, which allows for an immense range of potential immune responses. This section illustrates the complexity and the genetic underpinnings of our immune defenses.
🌟 Harnessing the Power of Antibodies
In this segment, the speaker discusses the process of extracting and sequencing antibodies from individuals who have survived various infectious diseases. He describes the procedure of removing white blood cells, sequencing them, and using the data to create a public database of antibody sequences. The speaker also touches on synthetic genomics, which allows for the reproduction of these antibodies in a lab setting, providing a potential source of treatment for current and future outbreaks. The narrative includes personal stories of survivors and the scientific efforts to understand and utilize their immune responses.
🌌 The Immune System: A Universe of Defense
The final paragraph wraps up the speaker's presentation by emphasizing the incredible capacity and complexity of the human immune system. He likens it to the vastness of the universe, with each person carrying an intricate network of defenses within. The speaker encourages the audience to face the future with a sense of confidence in the power of their immune systems, while also maintaining caution and wisdom in the face of infectious diseases. The summary serves as a reminder of the ongoing battle between pathogens and human resilience.
Mindmap
Keywords
💡Immune System
💡Infectious Diseases
💡Vital Signs
💡Vaccination
💡Antibodies
💡Genetics
💡Synthetic Genomics
💡Eradication
💡Pandemics
💡White Blood Cells
💡Cryo-electron Microscopy
Highlights
The speaker is a physician and scientist studying the human immune system.
Worked in a rural hospital in East Africa, witnessing the burden of infectious diseases on children.
A traumatic event involving the death of a child deeply affected the speaker and influenced their career focus.
The speaker vowed to dedicate their life to combating infectious diseases, especially for the most vulnerable.
Historical context provided on the impact of the Black Plague, 1918 influenza pandemic, and smallpox.
The eradication of smallpox through vaccination is highlighted as a major victory against infectious diseases.
Recent outbreaks of infectious diseases like bird flu, SARS, and Ebola are discussed.
The speaker emphasizes the importance of the immune system as the body's defense mechanism against infections.
A demonstration of blood cell observation under a microscope is conducted to illustrate the presence of white blood cells.
The Human Genome Project is mentioned, revealing the number of genes in the human body.
The complexity of the immune system, particularly the diversity of antibodies, is explained.
The speaker discusses the potential of sequencing all antibodies in the human population.
Synthetic genomics and the ability to create antibodies from DNA sequences are introduced.
Examples of antibodies derived from survivors of historical pandemics and their potential for future treatments are provided.
The speaker concludes by emphasizing the strength and complexity of the human immune system.
Transcripts
I'm a physician and a scientist and I
study the human immune
system now when I was a senior medical
student I worked for several months in a
rural Hospital in East Africa very
interesting place uh tea Farmers the kip
cigy people very beautiful and dignified
people but working in this place at my
young age was very challenging to me
because of the
overwhelming uh burden of infectious
diseases in young children
there and I had just learned to put on
my white coat and really my professional
demeanor as a physician in training but
an event happened very early in my time
there that broke through my shield uh
and shattered my world so uh I was
working on the ward the inpatient Ward
and every day we had about a dozen
children referred from the clinic for
admission to be admitted and treated in
hospital and I was along this Hall the
corridor and there were about a dozen
families waiting to be seen and as I
came in uh a man tugged gently at my my
coat and said sir would you see my child
and I turned to him thinking to say you
really need to wait your turn in line
sir when I looked over I saw his wife
was holding a small child and the child
was limp and somewhat blue looking and
this was very disturbing so we moved the
family very quickly into our procedure
room which was just really a closet and
the mother and father and I went in with
the nurse who is the translator now when
a doctor sees you uh at an exam the
first thing they typically do is take
Vital Signs and the first of those is
the pulse but in a child it's actually
easier to use your stethoscope to just
count the the heartbeat so I put my
stethoscope on uh and I was had the
child and I was really going to just
count the heartbeats and I was having
trouble with my stethoscope and they
toggle back and forth so I checked them
and just to make sure I had it in the
right place and I'm I'm listening and I
you know really I'm still having having
silence and then I realized I'm having
silence because the child does not have
a
heartbeat and at that moment in that
place with no ICU no life support all I
could do was to hand the child back to
the mother and say I'm so sorry your
child is
dead that mother let out a whale that
filled the entire room and the soul of
everyone who was there at the
time and something broke in my heart
that day I can't you know forget that
moment uh it start with me forever and I
was experienced in part by proximity the
sadness and loneliness that parents feel
when they experience the death of a
child sometimes when I would put my own
uh child to sleep I would kiss them and
and think about uh the child that died
in my arms and so I vowed in my bed that
night crying that I would use my life
and career to do something about
infectious diseases especially for the
most vulnerable Among Us and I would ask
you when you think about uh what's
happened in in history who is the more
formidable foe is it human beings or
pathogens now you know from your history
books about uh the black plague or
Bubonic plague starting about 1340 at
Peak about 2 million people a year died
um this is a painting from brole from
the 16th century this one on on a very
long time and I think most of us think
of the black plague as the most uh
impressive uh and horrific uh epidemic
that happened in history and certainly
it was
horrible uh but this seems uh long ago
and far away like a fairy tale of sorts
almost like it didn't happen uh but I
want you to remember that there are
people living today who were alive in
1918 when the 1918 influenza pandemic
occurred and 50 million people died in
one year due to that flu virus
interestingly people who are in their
20s and 30s were very susceptible during
this pandemic as well as in the
pandemics in 1957 68 and so on this is a
photograph from a makeshift infirmary in
a barracks in Kansas in the US during
the pandemic 5% of the US population
died that year 50 million people in the
world which far exceeds all of the
deaths in in the world war that was
going on at the time and so this is in
the memory of people who are living
today and at million people doesn't
impress you you may not realize 500
million people died of small pox and
recorded history now small pox is a
horrific disease it goes in every organ
of your body including your skin and
that's what you see these pox and a
third of the people who are infected die
now small pox is our first major victory
against an infectious Foe and how did we
do it we did it with vaccination uh we
used a weaken virus in a solution and
used a little forked needle and took
that needle and we pricked the skin
usually the skin of the arm 15 times
this video is actually me getting my
last small pox vaccine because we work
with similar viruses in the lab um so
I'm well protected against small pox if
it ever comes back but the thing is
small pox does not circulate in the
earth anymore because we eradicated so
we went from 500 million people dying to
no one dying not a single person is
infected with small pux and this is a
major victory but you have to realize
this only happened within the last you
know it's less than 40 years ago and
we've only done it once and it may seem
like a very uh crude way to fight but
this was the magic that allowed us to
eradicate infectious disease and we have
not been able to um do it again now the
who declared that small pox was
eradicated in 1980 and if you're a
millennial 1980 seems long ago and far
far away and kind of like a fairy tale
uh but if you've been uh watching the
news this keeps happening
1997 bird flu h5n1 Aven influenza SARS
2003 coming out in Asia very virulent
virus uh we just lived through the 2009
pandemic H1N1 flu Middle Eastern
respiratory uh syndrome virus in Saudi
Arabia very virulent virus chicken gunia
a million people in the Caribbean were
infected in one year in 20 14 with
debilitating arthritis uh you'll
remember watching the news with the
horrific outbreak of Ebola in West
Africa even came to the shores of the US
uh and last year zika virus sweeping
across South America millions of people
being infected including pregnant women
and the mosquito-born virus has
transmitted to pregnant women passes to
the fetus causing microsopy fetal damage
and death so this stuff is happening
every year around us and uh I want I
want you to think you know what are we
going to do about this uh what is the
what is the next step what are our
defenses and um I want you to just think
about your own body how do you think
about your your body and your health do
you feel healthy and powerful and
resistant or do you think of yourself as
somewhat vulnerable and susceptible and
at risk and when you think about the
entire human race are we resilient and
are we going to pass through all these
things or is there some fear
and and a realistic fear that the entire
human race could be eradicated by one of
these pandemics and I think you would be
justified given what I just showed you
to be concerned about that so the
question is what are we going to do now
when people think of their body um and
their health they often talk about
system they say well my system was run
down and I got a cold last week or I'd
really like to eat better and sleep more
build my system up and be strong well
what are you talking about when you talk
about a system what is that word what
you're really referring to is your
immune IM system your immune system is
your defense system that Wards off or
cures the infections after they happen
in you and I want you to think about
where is that immune system uh the
immune system traffics in all parts of
your body and it does that by living in
your blood so wonder if you ever
wondered what is in blood um maybe
you've never looked inside blood so
we're going to look today uh welcome to
my clinic uh I am actually the both the
physician and the patient
today and I'm going to draw my own
blood
ow uh we'll just get a little drop of
blood going
here so you know a a drop of blood is
just a tiny a tiny
little
volume but there's amazing let's look
and see what we've got
there so I have a uh this microscope is
wireless and my friends are going to
project me up here I think live and
let's see I've dyed this blood with a
blue dye there we go wow that's pretty
amazing so the little dark brown ones
here let me Focus this here are the red
blood cells and they carry the uh life
sustaining oxygen and the little ones in
the in the center that are blue they're
called the white blood cells if I if I
did put a stain you wouldn't see them
but see those two little blue
guys and then see if we can find some
more wow there's some more so those are
the white blood cells and Ted
fortunately has painted the logos for us
today so you'll remember this the red
blood cells are on the left and the
white blood cells on the right so
whenever you want to see that logo
you'll remember the two cells of the IM
of the blood
so um when I see these little blue cells
there's a lot of them in your blood just
just a tiny drop of blood and yet um
we see thousands and thousands of cells
but they all sort of look the same and
uh I've always wondered how many uh
different cells are there and really the
question is do we have enough tools to
um to defend ourself against all the
millions of microorganisms around there
is this enough these little blue dots
that are floating around in my drops of
blood how many do we have how many
different ones we have and uh so I
wanted to do a counting exercise and and
uh figure out how many parts of the body
there are in the immune system so when
we think about Parts uh scientists
usually these days are talking about
genes because in genes the genetic
material encode all your parts so we're
going to go back to the slides and I'm
going to give you a little genetics
class the uh Human Genome Project was
one of the major science projects that's
been done in the last several decades so
scientists spent about $3 billion doar
back in the day and uh took blood and
other body parts and sequenced all of
the genes in the human genome one of the
amazing things that that came out of
that project was that there are only
about 25,000 genes encoding your whole
body all your body tissues and organs
are encoded by just 25,000 genes
actually less than that and but uh that
number seems so small and not large
enough to deal with all the
microorganisms that we're going to face
in our life so it seemed a little scary
but uh what we didn't tell people was
that we of avoided the immune system
genes because there were so many of them
we were not able to get to them with the
technology at the time and the reason is
the molecules in your immune system that
help you fight things like viruses are
called antibodies and the antibodies are
encoded by combinations of genes so you
have these large buckets of genes
there's three main buckets or groups and
to make an antibody you choose one from
each bucket and you put them together
and by combining these things we get
this amazing diversity combinatorial
diversity is what we term and by doing
that we already have an immune system
collection that's as big as all the
other genes in your body but when we put
them together they don't go uh just end
to end they're put together with little
linkers or spacers and these spacers are
near infinite they're like having two
wild cards in your hand of uh your hand
of cards if you were playing cards and
by doing that we end up with 10 to the
11th possibilities of antibodies we can
make now we're talking real numbers and
real diversity and then finally we have
one more trick in our immune system and
that is in our antibody genes our
defense genes we allow those genes to
mutate when they see an organism and so
we get little uh point mutations so we
make new genes that are just a little
bit different from the ones we had
before now you wouldn't want to do this
in any of your other genes because you'd
end up with cancer but in the in the
immune system this is encouraged and
allowed and by doing that we get numbers
like 10 to the 18th are possible in your
body and I was really excited about that
um you can't get your mind around what
what is that number 10 to the 18th the
only thing I can say is you've heard a
lot of astronomy talks at this
conference you have more potential
antibodies in your body than all the
stars in the galaxy it's amazing and so
uh a lot of scientists like me have
obsessive compulsive Tendencies and they
like to just count things and a lot of
these star guys you were saying I want
to go out there on the shuttle and count
all these things well we have more
antibody genes than there are stars and
my friends and I want to count the 10 to
the 18th genes uh and how do you do that
well you do this with sequencing we have
uh instruments that determine the gene
sequences um so if if you were actually
going to count that many uh what would
you do so what I would like to do is
take all the white blood cells out of
your body and count every one of them
and sequence
them and you're giggling but that's
actually what we do so we bring in
people to uh our clinic at Vanderbilt
and we put them on the this instrument
that's like a blood filter we put one
needle in one arm and one in the other
the blood comes out we filter out all
the white blood cells into a large bag
there's 40 billion cells we collect into
these bags and we put the red blood
cells back in so that you can carry your
oxygen and you walk away you're not
anemic uh so you're fine and you'd say
wow that sounds very dangerous to to
remove all the white blood cells 40
billion cells from your body your body
is am amazing it can replenish those
almost immediately you make those back
and put them back so it's a very safe
procedure this is actually a friend and
a hero of mine Morris iuchi he's a
physician he was working in Legos
Nigeria during the Ebola outbreak and a
person came into the country and
basically lied about his situation he
had a bowl and showed up in the in their
hospital and Morris and several of his
colleagues took care of this patient and
they figured out it was Ebola and they
contained the uh infection uh within
their Hospital did not leak out in Legos
Legos has an unknown number of people
it's so large it's about 15 million
people if the virus had gotten out into
that high density population millions of
people would have died but Morris and
several of his physician colleagues
contained that in the hospital Morris
became infected while giving care to
these patients without any specific
treatment he survived uh and came to
Nashville and talked about his
experience and it was really just an
amazing talk about his courage and
persistence uh he survived he's fine now
and he came and gave us blood cells so
we've been studying people like Morris
extraordinary people uh who face down
these these
pathogens um and uh so what happens when
we take all these cells out we put them
in our expensive machines we get all
these sequences well DNA is encoded by
four letters g a t c so it's g g g c t a
a a t c and it just looks like this and
it's kind of like goly goo so what would
you do with that now if you're obsessive
compulsive you love these things and you
just kind of uh you sort of memorize
them how many can you memorize and my
friends and I are attempting at the at
this time to sequence all of the
antibodies on the planet in in the
entire human population and to put these
on a database publicly so people can use
them for their own studies now this is
an enormous task it's the largest
genetic project ever um ever attempted
and we've already started and we're
getting billions of sequences it's
really exciting but what would you do
other than just Catal in these things
it's just just an exercise in in
cataloging and Counting well it turns
out there's another Revolution going on
in biology it's called synthetic
genomics or synthesizing genes and
essentially we have little benchtop
instruments that are like DNA printers
so we can type in some letters and print
out the DNA and well so what about that
well if I type in uh the sequence of an
antibody that I got from Morris's body
that's for Ebola that machine will make
me that DNA I can use that DNA as the
recipe to make the antibody that he was
making in in his body I can make it in
the lab so then we end up with tubes
full of antibodies that are the natural
antibodies from his body but we can make
them forever in unlimited quantities and
give them to other people so it's really
fun to make antibodies it's sort of like
having a little Play-Doh Factory and you
can make uh make things all day
long so I'll give you some examples I
mentioned there are survivors from the
1918 pandemic we've learned a lot of
things one is that your blood retains
the memory of everything you've ever
seen in your experience so uh we
obtained blood from 100-year-old
subjects who had experienced 1918
infection and we were able to get
antibodies out of them that kill the
virus so this is a highresolution x-ray
crystallography structure but basically
you're seeing a single molecule of the
flu protein in the middle and on the top
and yellow and red are antibodies from a
100y old person that bind to and inhibit
1918 flu once we learn we could do it
100 years later everything else seemed
easy here's another example Michelle
barns an adventure traveler went to
Uganda with her husband they were on
Safari seeing amazing animals and the
guide said wow if you like these animals
you should go in Python cave with us on
the last day there this cave has 40,000
fruit bats in it and they're amazing and
Michelle did go in that cave this is a
photograph of the roof of the cave taken
by another friend Joel S he's a National
Geographic photographer a fantastic
photographer this is the actual cave in
which she entered she went to kalala
flew home to the Denver area and about a
week later she nearly died no one knew
what was happening to her she recovered
of her own accord no specific therapy
and a year later it was discovered she
had had marberg Virus Infection marberg
is a deadly cousin of Ebola it's very
similar to Ebola so she was the only
known marberg Survivor at least in the
Western Hemisphere she talked about her
experience at Ted axe Boulder last year
was very very exciting to hear we took
her blood and made a large number of
antibodies this is one of them so in the
center is the marberg protein from the
virus and her antibodies are shown in
yellow we isolate a lot of antibodies
and they'll actually inhibit and kill
the marberg virus so this particular
antibody these antibodies are being
developed in fact the United States
government just invested $30 million to
uh further develop this antibody as a
therapy for the next cases of marberg or
if an outbreak occurs another example
would be zika virus we uh worked with uh
a person who had been infected in South
America last year got cells out made
antibodies here you're seeing the
antibodies in red and this is called a
cryo electron micrograph but it's just
one virus particle it's a picture of one
virus of zika a zika particle and it's
decorated on the surface by the red
antibodies which are attaching to and
killing the virus so in summary when we
when we think back to uh my question
who's who's the a bigger foe is it
infectious diseases or is it you and
your immune system and I hope it's
obvious to you the amazing depth and
complexity and beauty and Glory of what
is within you the human immune system is
the most deep and Rich information
system on the planet and each one of you
have it within you so when you think
about the future I want you to walk
boldly into your future with caution and
wisdom of course but be confident of
that glory and complexity that is the
universe within you thank
[Applause]
you
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