Harper Lecture with Jack Gilbert: Adventures in Our Microbial World

By Adem Lewis / in , , , , , , , , , , , , , , , , , , , , , , , , /

Good evening. I’m Tracey Pavlishin. I’m the Executive Director
for Campaign Management at the University of Chicago. I’m also a proud graduate from
Chicago Booth, Class of 2006. Thank you for coming tonight
to the eight event in the fall Harper Lecture series. We started in Chapel Hill. And we are concluding
in Mumbai next month. Tonight’s event in Boston
is the eighth in our series. And in fact,
technically it’s tied, because we already had an
event in London earlier today. And we’re having another
event in San Francisco. I hope you’re
enjoying the chance to connect, or reconnect,
with the University of Chicago and with one another. So I’m here to talk about the
University of Chicago Campaign Inquiry and Impact. Before I do that,
I’d like to share with you what’s been
happening on campus this week. It’s Homecoming week. And on Monday we distributed
nearly 1,000 t-shirts to students to help–
on Maroon Monday– to help Chicago-ize
their wardrobe. We also had a special
Homecoming shake day. And right now, over 25
student groups and houses are painting banners
at Henry Crown Field House in preparation for
the annual Homecoming banner competition. And this weekend,
we will welcome over 4,000 families, alumni,
faculty, staff, and students to campus for Homecoming
and block party festivities. And while you can’t attend
in person this year, I hope you’ll consider
returning to campus next fall to join in the fun. These activities, and many
more, are planned for this fall to help celebrate the
University’s 125th anniversary. Our University was founded
on the basis of philanthropy. And the University of Chicago
Campaign Inquiry and Impact honors this milestone
and tradition. We want to engage 125,000
alumni with the University. And of course, we also
want to raise $4.5 billion. [INAUDIBLE] what? [LAUGHTER] I’m pleased to share that so
far we have raised $2.7 billion towards this goal, and
engaged nearly 56,000 alumni who have made a donation,
attended events, volunteered, or participated in
social media channels. As a Booth Alum, I love data. So let me share
some stats with you. Engaging 125,000
alumni represents 80% of our population. So this is truly
an ambitious goal. Massachusetts is home to
5,000 alumni, 4,000 of which reside in the Boston
metropolitan area. 34% of our alumni here are
graduates from the College, 24% from Chicago Booth, 11% from
the social sciences division, and 6% each from the law school
and the division of humanities. 56% graduated since 1990. And by 2019, which is
the end of the campaign, our target is to engage
3,425 alumni from Boston. We are 47% towards
that goal already, with 2/3 of this engagement
coming from donations. As you know, it’s
important for alumni to engage with the University
on multiple dimensions to help strengthen and extend
a powerful network that fosters personal satisfaction
and professional success. Your attendance tonight is a
great step in this direction, thank you. So I’m asking you, if
you haven’t already, to please consider investing
financially, serving as a mentor, hiring an alum,
volunteering with the alumni club, and connecting with the
University on social media. We have a very fun
photo booth over here that I’m happy to
say does not reflect today’s current weather. So after the program
today, I hope you’ll go over there and
take some fun pictures and imagine it being
cold since it was well over 70 degrees here today. And as President
Zimmer says, we are asking you to do still more so
that the University of Chicago, in the coming decades,
will succeed far beyond reasonable expectations. Thank you for coming tonight
and please enjoy the event. [VIDEO PLAYBACK] [MUSIC PLAYING] The University of Chicago is– –urban– –global– –courageous– –unusual– –phenomenal– –rigorous– –fabulous– –outspoken– –economics and pizza– –pushing borders– –invigorating– –an intellectual crucible– –that pushes you to
be your best every day. From its inception, the
University of Chicago focused on rigorous
intense inquiry. It’s defined everything about
what the University of Chicago is today and what it
will be in the future. The core curriculum is
a symbol of who we are. Our mission is to get
very talented students, and to put them
through a program of systematic,
interdisciplinary training. And four years later, graduate
Chicago intellectuals. I’ll bring up a discovery
that we’ve made. Then I’ll proceed to
criticize my own discovery. It’s through self-criticism
you create a learning culture of critical inquiry. We aren’t just
talking at each other. We’re listening. And at the end of the class, I
may have a completely different perspective on the issue. Some excellent, excellent
students over the years. They were very much my teachers. It changed my work. Or it just exposed me
to a world of ideas. I was the beneficiary
of the scholarship from the University of Chicago. I could not have gone
to business school without that scholarship. I just feel so grateful
that I was selected to kind of be among the
minds, and the intelligence, and the incredible people. It’s been the best
experience of my life. I think supporting young
people to pursue their dreams opens up the world to you. All we ask of anybody
is that they do the same to the next generation. The University is really
made by the people in it. Really very competitive. Very unruly. Seeing all the crazy, amazing
things that they’re doing. Curing diabetes, cancer. Innovation, more
entrepreneurship, new ventures, new technologies. It really forces me
to push for something beyond what I’m doing. In higher education
today, the humanities are really in retreat. We really think that
it’s a responsibility to continue to foster
growth of the humanities. A collegium will allow
teams of humanists from all over the world to
tackle problems that society needs to deal with. The Institute of
Molecular Engineering is organized around solving
water, energy, health problems through designing
matter from molecules. Just solving one of all of these
problems they’re working on would be tremendous. They’re part of an
intellectual community that attracts individuals who
are intellectually fearless, that will bring together experts
from different disciplines to help solve problems. We’re exploring
opportunities to create more portals for the community,
and the people in the city to come into the University and
both get some of the knowledge that we have, but also share
their knowledge with us. Lots of people are
skeptical about the ability to use social programs
to prevent crime. What we’ve tried to do
is to generate evidence that is so rigorous
and so compelling that the most
skeptical skeptic will have to acknowledge that
there’s really something here. One year of participation
in the Youth Guidance’s Becoming a Man program
reduced violent crime arrests to these kids by over 40%. Which I think really challenges
the conventional wisdom that the only way that you
can control crime and violence in the United States is
through locking up millions and millions of people. And if you show the impact,
it has global reach. Billions of people,
not just millions, billions of people
that you can get to. It’s very important,
in a world which is becoming more
integrated, that you have these global universities. We now have a rather more
ambitious global strategy with the same gold
standard quality of curriculum and teaching. Students are going to want the
experience of understanding other cultures. Because this is going to be the
world that they are functioning in over the coming decades. Can we bring people, scholars,
politicians, administrators from these different
areas also together to discuss what’s going on? To debate the big
challenges facing the world. Human illness limits society. And accordingly, fixing
that, addressing it, is hugely important. It’s transformative. I had been diagnosed with
metastatic or advanced breast cancer. The first thing Dr.
Olufunmilayo Olapade said to me is, I want to find
out more about your tumor so that I can personalize
the treatment for both you and the tumor. The survival rate for metastatic
diseases was one to two years. I really must say that I
have survived the odds. I mean, I’m still sitting here,
standing here, 10 years plus. You know what, it’s worth
every day, getting up, I’m supporting
patients like her. We have an enormous
obligation to the people who gave us the opportunity
today to do what we do with these young people. And in turn, they
have an obligation to support those
who come after us. The question for us
today is how do we realize these values in a
powerful way going forward? Together, we are spreading
grace and humanity. Together we are– Thinking about ways in which you
can have an impact on society. Together– We have the potential to
change the way people think about urban problems. Together– We make amazing
discoveries possible. It’s part of our DNA. It’s who we are. It’s a big, big universe here. Ours is the University
of great discoveries. Ours is the University
of fearless inquiry. Ours is the University
that develops ideas that change the world. [MUSIC PLAYING] [END PLAYBACK] Good evening. I’d like to extend a
welcome to all the alumni and guests to this
evening’s program, and also extend a special
welcome to our colleagues at the Marine
Biological Laboratories. I am Rene Mora. I am a graduate of the
Biological Sciences division. I graduated in 1988, and the
Pritzker School of Medicine in 1989. Currently, I’m the
Chief Scientific Officer at Leerink Partners. I’m also the immediate
past president of the Alumni Council of the
Medical and Biological Sciences Alumni Association. Just a reminder, that
the Alumni Council consists of 32
alumni volunteers who work to provide services
both to existing students and alumni of the divisions
and the School of Medicine, and also to strengthen
the connection between the– strengthen
the alumni community and the connection between
alumni and current faculty. For 125 years, the
University has a tradition of both attracting
and supporting faculty that does
transformational research. And the Harper Lectures
reflect the– also reflect the tradition of
bringing alumni and faculty together to celebrate the work
that happens at the University. So without further
ado, it is my pleasure to introduce Dr. Jack Gilbert. And I will have to read this. Dr. Jack Gilbert
is the group leader for microbial ecology at
Argonne National Laboratory, Associate Professor of
the Department of Ecology and Evolution,
Associate Director of the Institute for
Genomic and Systems Biology, and Adjunct Senior Scientist
at the Marine Biological Laboratory. He’s authored more than
150 scientific papers on microbial ecology in a
variety of environments, including our built
environment and the human body. So his research
explores the interface between the microbial
world and our lives, and does it in such a way
that it blurs the distinction between different ecosystems. Regarding the work that Jack
does at the Marine Biological Laboratory– just
again, for those of you who are not fully
aware, he works within the Bay Paul Center
for Comparative Biology and Evolution. The Marine Biological
Laboratory has been affiliated with the
University of Chicago since July of 2013. And the work that
Jack does at the MBL is an excellent example of the
kinds of exciting partnerships that this affiliation
is making possible. So tonight’s lecture will be
Adventures in our Microbial World. And in this lecture
he will explain how micro-organisms in
the various environments shape our health
and development. So there’s a complex,
emerging, new human ecosystem which may be both the
source and the solution to modern health concerns
including depression, anxiety, allergies, and autism. Dr. Gilbert. [APPLAUSE] It’s my great
pleasure to be here. I never get to come
to Boston and actually look around Boston. Today hasn’t been any different. I came into the hotel, and
I sat in the hotel room, and I miss that opportunity
every single time. And the cameraman is
going to get upset with me if I move around too much. So I have to stand in this
nearly exact location. And that’s going to be
really pertinent to you three people right there. I’ll explain it. So I’m a microbial ecologist. I’m also English. Not British as some
people might think, I have nothing to do
with Scotland or Wales. It’s just England. But I am very interested. I came here in 2010. I was a joint appointee at both
Argonne National Laboratory and the University of Chicago. And then when we
partnered up with the MBL, I became a triple threat. So the University of Chicago,
or Argonne, or the MBL depending upon what your
flavor is of the week. And the MBL is actually a
fantastic opportunity for me because I’m actually a marine
[? microbial ecologist ?] by training. I worked for a private
consulting firm in the UK before I came back
into academia. And [INAUDIBLE] working
with bacteria in the oceans. And so for me, when
we acquired this, I was like, wow,
this is awesome. We got the MBL. This is– I mean not acquired,
partnered, sorry, partnered. This is awesome. It’s brilliant. I’m really excited. So I threw myself into
the crucible of the three institutions that are now
trying to bridge the gaps by, as you so eloquently
said, blurring the lines between
our ecosystems. If a marine microbial
ecologist can start working in the bacteria
that live inside our body, that means I can work in pretty
much any environment in which I find bacteria. And luckily for me, that’s
all environments, everywhere, right? Because they’re so pervasive. But the human body is still a
fascinating ecosystem for me. It’s an ecosystem
which is fundamentally evolved in a sea of microbes. OK, you know, if you think
about multicellular life crawling out of the
oceans, that was about 400 million years ago. And Neil Shubin
constantly reminds me that that’s still an important
fact that I have to deal with. If you ever watch
his show, by the way, it’s brilliant, Your Inner Fish. These organisms that we
call– well these beings that we call
humans– I often come from the microbial perspective. You know, you have to
understand that for me, that’s my fundamental level. Everything else is just
blurry lumps of matter. But this lump of
matter is involved in a microbial context, right. The body could not
keep bacteria out. It could not keep
viruses at bay. It was technically
impossible for the organism to evolve mechanisms
to do that properly. So it evolved techniques to
integrate microbial ecosystems into its body. It evolved mechanisms such as
innate and adaptive immunity. The brutal force approach
of innate immunity to kill everything randomly,
and the adaptive capabilities of adaptive immunity
to evolve to look at the particular
organisms it wants to kill and the particular organisms
it doesn’t want to kill, it wants to keep around. But the problem is, we’ve
evolved those mechanisms because we were constantly
being bombarded and exposed to many, many different forms of
bacteria, many different forms of viruses. But now in our modern world,
we’ve reduced that exposure. And then, what
we’re looking at now are the ways in
which that disruption of our interface
with the environment has somehow impacted our health. And it’s– we’re seeing
it all around us, and in many people that you’ll
know who have food allergies, who have neurodevelopmental
disorders such as depression, and anxiety, autism,
and Parkinson’s. These are people
who have potentially had a triggering event
through a disruption in their microbial selves. Now we have 100 trillion
of these bacteria living inside us. That’s about three pounds of
bacterial biomass, most of it centered here in your gut. And that is the same weight
as your brain, bear in mind. You’ve got the same weight
of brain is in bacteria. And if you removed
all those bacteria, you’d survive as
long as you were kept in a little bubble
completely isolated from the rest of
the world, you know. And we do that to animals. We call them germ-free animals. We take all their bacteria away. But when we do that, we take
a bacteria– like a mouse, and we take all of
its bacteria away, it grows up
physiologically disturbed. So this is the healthy
cecum of a mouse. It’s the part of its gut that
contains most of its bacteria. And if we grow a mouse
without bacteria, its cecum looks inflamed. It looks enlarged, OK? Its gut looks significantly
different to the way it does when the bacteria are present. The removal of
those organisms has caused physiological
anomalies in the development of that mouse. And it’s not just
in its physiology, it’s also in its neurology. Aw, OK, I’ll come back to
that because that’s cool. Yes, I did only prepare
my slides– no, no. Its neurology is also
a significant component of that disruption. This is a great example. This is an elevated maze. The platform is
about a meter high. And either side of that
platform we have a little box. If we place a normal
mouse inside that box, it’s going to do one thing. It’s going to hide. It’s going to stay
inside that box. It’s going to hunker
down because it’s anxious about showing itself
to the rest of the ecosystem, right? And that’s for a good reason. The mouse that stayed
hidden didn’t get eaten. And therefore, it gave
birth to more mice. And that progeny lived on, OK? And you evolve a– through
selective adaptation, you evolve a mechanism
of anxious activity, OK. If we take all the bacteria
away from the mouse, we’ve got a germ-free
mouse, that mouse loses all that anxiety. That mouse then becomes
neurologically disturbed compared to its natural
phenotype, right. This mouse is no
longer behaving the way it should behave in
their native world. That’s because the bacteria
in the gut of this animal are communicating
with the brain. Through the release
of certain chemicals, through stimulation
of the immune system, through the interaction
with nerve endings embedded inside the gut
wall, the bacteria are actually sending signals
in a near continuous fashion to the brain. The part of your
response mechanism to satiation after you’ve eaten
enough food, you’re now full, is actually due to changes in
the immune profile of your gut. Because the bacteria are now
responding in a different way because the system is being fed. And that sends nerve impulses
up into your brain which changes your appetite, right,
you’re no longer hungry. Well this is
constantly happening. And when you have certain
types of bacteria missing in this environment, it
sends aberrant signals up to the brain, and
aberrant signals to the rest of the
body which can change the way the body’s responding
to this environmental stimulus, OK. So in the mouse model this
is particularly prevalent. A mouse can be
made to be anxious, or made to be non-anxious
based on the presence or absence of bacteria. But in humans, it’s the
opposite way around, right. Our native state is probably
not anxious and severely, cripplingly depressed. But the absence of
certain organisms may be inducing that state. And a lot of my
research is focused now on trying to uncover
that mechanism by which the disruption of
bacteria inside your body influences your potential
depression phenotype. We look at this is especially
in pregnant women, so perinatal and
postnatal depression, and in post-surgical depression,
and in mechanisms whereby depression treatments
such as antidepressants, selective serotonin reuptake
inhibitors, and the like, when we consume them,
whether they have an influence on
[INAUDIBLE] or not is changed by the types of
bacteria we see in our body. So actively trying to
uncover that mechanism is a key component
of our research. I’ll go back to this
because this is cool. So bacteria can induce
allergies in our body. And we don’t know why. Working with Cathy Nagler at
the University of Chicago, we’ve started to uncover that
the environmental exposure that we get inside
an environment is significant lower, probably
because of all those cleaning products and the rampant
use of antimicrobial agents. And that might– that’s led to
our healthy microorganisms that are normally associated with
our body being disrupted, OK. And they’re
potentially leaving us open to allergies, and asthma,
and various other conditions. And what we’re looking
at is how to reinforce the healthy microbiome
inside the body of children so that they are no
longer allergically over-responding to
particular conditions, or particular stimulants. So we now have a food allergy
research and education network at the University of Chicago. And we’re actively utilizing
that to take the research out of the lab and put
it into the clinic where we can actually help
children as soon as possible. And this is fundamental. The acceleration
of getting research into a form which is practicable
and helps people as quickly as possible without being
held up in red tape, is fundamental to
advancing medical science, and balancing any
kind of science. And we’ve been really key at
the University of Chicago, and at the Marine Biological
Lab, and even at Argonne, in trying to get scientists
like myself to integrate with industrial
people, so people who are working in companies. I’ve actually started up
two of my own companies off the basis of that
by trying to develop commercial applications
for my own research. I’m not going to talk about
those because that would be a conflict of interest. But, if you’re interested,
come and nudge me afterwards. Bacteria can make you
obese, or make you fat. One of my friends,
Liping Xiao, he used to be a very
heavy-set guy, 385 pounds. And he lost 113 pounds by
going on a traditional Chinese wholegrain diet. It’s not a particularly
pleasant diet. But you know, it works. And it’s been shown to
work for hundreds of years. And by doing this, he actually
changed his microbiome. His bacteria were
different in the beginning to the way they were at the end. Oh course, you know,
you’re changing the ecosystem inside you. You’re adding different things. Before he was eating a
lot of fats and sugars. And now he’s changed
it to a different type of composition, mostly fiber. And that’s altered
the ecosystem. And with his ecosystem altered,
the players inside him changed. One particular organism,
enterobacter cloacea B29– which is really abundant when
he was on a heavyset diet, like a high-fat,
high-sugar diet, was absent at the end
of his whole grain diet– seems to be able to
induce obesity in a mouse. We cultured that out of Liping’s
stool from when he was obese. And when we culture it
and put it into a mouse, the mouse gained
significantly more weight than when the mouse
didn’t have this organism. And this is the
mouse without it. This is the mouse with it. So the introduction
of one organism can somehow concomitantly
influence the obesity phenotype in a mouse, OK. Now this is true
whether you have a germ-free mouse
or a mouse it’s already got bacteria inside it. So even if I add–
if the only bacterium present inside that mouse
is enterobacter cloacea B29, it will still put on more
weight for the same amount of calorific intake, OK. But if it’s got a lot of
bacteria in there already, then the addition
of this organism can disrupt the phenotype
of the mouse, additionally, still causing it to gain weight. This is a great study from
Ruth Ley’s lab up at Cornell. But I like to highlight
it because it’s the opposite side of the fence. In monozygotic and
dizygotic twins, you actually have an
interesting phenotype. Monozygotic twins have a
more similar microbiome– these are identical twins–
a more similar microbiome than people who aren’t
genetically identical. She’s not– it’s not
the way you think though, these
people aren’t still microbiologically identical. They’re actually
microbiologically still unique. I can tell each one of
those twins apart based on the bacteria
living in their stool. And I can do that for every
single one of you as well. And that will be
important later. Yeah. But what’s interesting
is, if I have a genome of every
single one of you, I’ll be able to
predict whether you’re going to be obese or not with
about a 50% accuracy rate, right. So I’m– your genome is not very
good at predicting whether you are going to be obese or not. It’s not necessarily
in your genes, OK? So you do have that
situation where you have monozygotic twins,
one of whom is obese, and one of whom is lean. And when you look at
the microbial profile between those two individuals,
who are obviously controlled for their genome,
and the lean twin has an abundance of
organisms belonging to a family of bacteria called
the Christensenellaceae. These organisms show a
high hereditable function. It looks like they’re
passed down from mother to child, mother to child,
mother to child, ad infinitum, OK. So we’ll talk about how
that happens in a minute. But what’s
interesting is, if you do this experiment– this is
one of my favorite experiments of the last recent
years in terms of proving this as
a study– If we take the stool bacteria from an obese
twin and we give it to a mouse, the mouse gains more weight
for the same calorific intake, exactly the same as we
saw with Liping’s study. There’s something in
the bacterial population present in there, that
is inducing obesity. Interestingly, it’s not
enterobacter cloacea B29. That’s not the only fat
inducing bacterium out there, there’s lots of others. What’s interesting is if you
take the same stool sample, the same bacteria, but you
add Christensenella minuta, one of these
organisms that shows a high propensity
in lean people, the mouse won’t gain weight. Christensenella minuta
actively dampens down that obesity response. It protects the mouse
from becoming obese on the same calorific intake. So one bug makes you fat. One bug makes you thin. You can get this bug– if
you could put it in a bottle and sell it in Whole Foods,
you’d make a million dollars overnight. It would be amazing. But it’s not as
simple as that, right. Actually the probiotic market
is entirely unregulated. Anyone who’s interested
in making some money, it currently is– it’s
very easy to just put something in a bottle. In our lab, we went in and–
we went into Whole Foods once and, in a totally
unscientific manner, just bought 30
types of probiotic. And Jarrad
Hampton-Marcell, in my lab, sequenced the bacteria
that are present in there. In the vast majority of them, it
wasn’t what it said on the tin. You know, it is a really
unregulated market. Anyway, this is for
high importance. This means that we
could potentially have a microbial response
that protects people from becoming obese. And where do those
bacteria come from? Well there’s another
part of this story. And this is a
study– actually one of the guys involved
in this study is present in the
room, Sean Gibbons, who is one of our alums that’s
now doing a postdoc at MIT. And I’ll call him out a bit. In this study, we looked
at how the bacteria in the gut of a– a
mouse in this case– responds to a change in diet. So we know when we change
the diet of Liping, certain bacteria disappeared. We went from an unhealthy
diet to a healthy diet, he lost some of those
obesity inducing organisms. What happens when
we give a mouse a load of high-fat,
high-sugar diet, it changes the microbial
ecosystem inside that mouse. And it doesn’t just make
some organisms disappear, it also makes the rhythmicity,
the temporal daily pattern, how it changes day to night,
of that microbial community. The microbial clock inside
your gut becomes disrupted. It no longer follows
a nice flowing pattern like the rest of your body. It follows a very
disrupted pattern. And you have clocks
throughout your body, OK. You have clocks in pretty much
every organ inside your body, and especially in your brain. The one in your brain is mostly
altered by the amount of day and night you see. So if you are
chronically jet lagged, or you’re working
nights, you’re going to have a disrupted circadian
rhythm, a disrupted clock inside your brain, which
alters your body chemistry, OK. And we see this. If you are working nights,
or you are chronically jet lagged– I’m one of those
chronically jet lagged people. I’ve got a flight
to China tomorrow– you actually put on more weight
for the same calorific intake. It’s not all those business
dinners and lunches, it’s just– anyway,
it probably is– but it’s your body
being disrupted by your time-keeping
mechanism inside your body. So what happens is,
when we actually give this mouse a load of
high-fat, high-sugar food, that’s exactly the
same thing as if you put the mouse through a
disrupted sleep cycle. That somehow, the
disruption of the circadian rhythms, the rhythmicity
of the clocks inside your bacteria
inside your gut actually affect rhythmicity
of clocks inside your liver. And rhythmicity in
clocks inside your brain can also fall out of sync with
the ones inside your liver. And this actually causes your
body to put on more weight. We’ve uncovered a
mechanism– this is work at the
University of Chicago– by which diet induces
obesity in the body. By altering the chemical
phenotype and the clock genes inside our body, our
body then is disrupted and puts on more weight at
the same calorific intake. Now I asked you where
those bacteria come from. The first one is from
your mother, right? If this is your starting
culture, your sourdough bread if you will, your
mother gives you bacteria via one of two roots. If you are born via the
traditional, native, natural route, you get your
mother’s vaginal microflora as your starting culture, right? That’s where you
evolved, remember. You evolved to be
delivered vaginally. And your body evolved
to see those bacteria in its first weeks,
months, years of life. And these bacteria stay
with you for like a year and a half or more. Some of them can stay with
you for the entire period of your life. If you’re born
cesarean section, you look like mother’s skin, or
the skin of the first person you come into contact with. It could be father’s skin. And those skin bacteria colonise
the child inside and out and fundamentally alter
that starting culture. In ecology, we have something
called the founder effect. Much the same way as if it
hadn’t been the Pilgrim’s that got to Plymouth Rock, if it
had been some German sect, it would have been a very
different world, right? And the founder effect
changes the progression of the ecosystem development. So the ones that start out
being there in the beginning can alter what happens later. And there is some evidence
that this disruption between cesarean birth
and vaginal birth could lead to other phenotypes
later in life like obesity, even your developmental
conditions, even autism, and asthma. And that’s correlative. There’s no actual direct
evidence of it at the moment. The disruption of this
very early in life from the use of
antibiotics early in birth, and we were talking
about this earlier, can lead to a
significant disruption in the types of
bacteria we see, which can also have concomitant
effects in that space. But, there’s a way
to get around that. Obviously, sometimes you have
to have a cesarean section. You can’t avoid it. So, they’ve– one of
my colleagues developed a technique or adopted a
technique whereby you place a small sponge inside
the vaginal cavity during pregnancy– during birth, sorry. And then you literally
hand colonize the baby with that sponge afterwards. It sounds pretty gross,
but it’s actually an effective way of getting
the right kinds of bacteria into that child at
the starting point so it can develop normally in
the way that nature intended. Your breast milk also has
its own microflora inside it. And so this is another
important point. Mothers seem to actively
recruit bacteria from the gastrointestinal
cavity into the breast milk, and that then becomes a
probiotic delivered by mother into the baby’s gut. That probiotic, those bacteria
inside the breast milk, are actually perfect
for digesting, perfectly capable,
perfectly adapted to digest the kinds of sugars
and lipids and proteins you find in breast
milk, almost like it was like planned somehow,
or evolved in that way. And then, what’s remarkable
is those bacteria are also very good
at stimulating early immune
responses in the gut. So we see that
positive influence. Now is not the only story. We also are very affected
by the environment in which we live in. So as I said before,
the environment which we live in now is very different
than the one we grew up in. We have a great story of the
Amish and the Hutterites. Both of them come from the
same place in Eastern Europe, the same ancestral lineage. But the Hutterites have
massively elevated asthma over the US average. And the Amish have virtually
none, no asthma at all. And the Amish live on their
own individual family farms, and constantly exposed to
the kind of environment their ancestors grew up in,
a family farm environment where they’re interacting
with the animals from birth. The Hutterites live
on big communal farms where only boys
over the age of 14 are actually
allowed on the farm. So as children, none
of them get exposure to the kind of
farming environment– it’s great– farming
environment that the Amish do. Sorry, I was being signaled. I’ve got to hurry up. I get really excited
about this because it’s a really exciting topic. And then I go off on tangents. I got to be careful, anyway. So we think that that
early life exposure to the kind of environment your
ancestors were being exposed to, and the kind of bacteria
they were being exposed to, may have a significant
influence on determining whether you’re going
to develop these kind of autoimmune conditions. And the environment that
you and I grew up in is no better, probably
worse than that of the Amish– of the,
sorry of the Hutterites. It’s the built environment. In this room right now,
the air is being very well climate-controlled,
it’s being dried, it’s being a
temperature monitored. And it’s not a particularly
great environment for bacteria to survive and thrive in. In fact, we’ve done
a really good job of making sure this environment
is clean and sterile as possible. That can change
sometimes with funguses. But when we look at the bacteria
we find in this environment, it’s mostly from people. It’s mostly from people’s skin. Even when we go into the
international space station, the bacteria we find up there up
are from the astronaut’s skin. And this is the
environment in which we’re bringing up our children. I took my first and
second son’s home, and I brought them
into an environment where the only real microbial
exposure they were getting inside the house was from the
bacteria that were coming off of my skin, and their
mother’s skin, and their skin. And this fundamentally alters
the trajectory of succession. Because they’re not
getting that complex, rich exposure from the
environment, which they, theoretically as a species,
evolved to acquire. And so we’re very interested
in this built environment and how that microbial
transmission may be affecting the development of people. In the Home Microbiome
Project, we actually looked at how bacterial
interactions with our home fundamentally altered with
different family units. So if you had four
people in the family, or one person in the family,
or a big, complex family, it can alter how the
microbial transitions and how microbes move
around that environment. And that could
fundamentally alter the development of people. But we found something
even more interesting that I’m going to
talk about right now. That the bacteria we
left behind was entirely unique to the individuals. Take these two environments,
the kitchen counter and kitchen floor. This is time. So we took samples
every day for six weeks. Person– this is a
family with three people and three dogs, two grown–
two parents and one grown child and three dogs. We look at the kitchen counter,
it’s mostly person three. There’s no gender
bias here, but it was the mother in the family. And she did spend a lot
of time in the kitchen. Apart from when she
left for a while, and person two’s–
[INAUDIBLE] left for a while, and person two’s
microbiome took off. That was the father
taking over the cooking because he had to
fend for himself. And this is highly important. We can actually identify
these kind of activities. We look at the kitchen floor,
though, it’s mostly dog. The dog bacteria are
colonizing it’s surface. This is important. If you’re an infant crawling
around on the floor, that’s going to be your
exposure in an environment. And that might
sound icky, right? Like dog bacteria are
dangerous because dogs are smelly and dirty. And we should protect our
children from those bacteria. I’m going to show you that’s
not necessary the case. This whole idea has led the
concept of the microbial cloud. This is the bacteria
we give off. This is Pig-Pen. And Pig-Pen gives off
a lot of bacteria. If I walk– and I’m
not allowed to walk– but if I walk like
this, I’m actually shedding bacteria, around
32 million cells an hour into my immediate environment. This blurs the line between
your body and the environment you’re living in. Because you’re constantly being
colonized and shedding bacteria into this space. And that means that if you’re
sitting closer together, your microbes are
being more interwoven. And actually, you
guys are probably getting a lot of my oral
bacteria, right now. And I apologize for that. Some mice bacteria. Yeah maybe, yeah. But it means that we can
track people’s behaviors because as they interact,
as they physically interact, it changes their
microbial flora. So this is a young couple
living with a lodger. And these are microbial samples. The closer the dots are
together, the most similar they are. And over here on
the left hand side, you can see that
the young couple are very microbiologically
similar, much more so than they are to the lodger. This is because the young couple
are physically interacting. And they’re exchanging
microbes much more frequently than they are with the lodger. But the lodger is still more
microbiologically similar to the young couple, because
he lives in the same space, than he is to anyone
else in our study. And we’re utilizing this
to develop new crime solving techniques. And hopefully we’ll
find some criminals. But, I don’t know if this
is the right audience. I’m English, I stay
out of your politics. We actually went down–
we’ve been working with police departments around
the country in very warm places like Florida and Hawaii where
we can go in the winter, in order to actively
develop, with the National Institutes of Justice and
the Department of Justice, the microbial fingerprint you
leave behind as a technique. So we’re currently funded
by those organizations to work with the PD and
with their forensic units to figure out ways– this is
Jarrad Hampton-Marcell, who works in my lab–
figure out ways to capture the bacteria
that are present on surfaces after a burglary has happened. We got two students to burgle
this house– yeah, all right. They’re very
particular about time. And when those two
students burgled the house– it wasn’t
a real burglary, we set it up– we then
went in straight afterwards and we sequenced the
microbiome of all the floors and surfaces which they may
have come into contact with. And then what we did is we
sequenced the microbiome with the residents
and their cat. And we extracted, we
removed that signature of the residence and
the cat from the stuff that was left on the floor. The residual microbiome
we could find was human. And when we ran it against
our database, which luckily contained our two
students, we could identify each of those
students with a 99.3% accuracy. But let’s say they’re
not in our database. One thing we could uncover
about those two students is they both drank heavily,
like 20 units a week. I don’t know if that’s heavy. It doesn’t sound
heavy, but anyway. And one of them took
migraine medicine. Because both of those
attributes, both those lifestyle choices,
changed their microbial flora to such an extent that it left
a signature of the microbes they left behind. So this is very
important in trying to develop new therapies. Now we can map the
microbial profile. This is my family. Very obvious, the feet
interact with the floors, and the hands
interact with surfaces you touch with your hands. If we add dogs into that
environment, it goes crazy. The microbial interactions are
significantly more detailed. We know that couples
that live with a dog are more microbiology
similar because the dog is promiscuously sharing microbes
in a much more rigorous way. This led to me– we rescued
a dog from Kentucky. He was in a kill
shelter as a puppy. You think he’s cute now? You should have
seen him as a puppy. Anyway, we rescued him. And he’s now been
sharing our microbes and sharing them around our
environment in a rigorous way. And this is a good thing, right? That kid crawling
around on the floor, getting that microbial
exposure from the dogs, may actually be picking
up particular dog bacteria such as lactobacillus. Which, when entered into
a mouse model at least, show a significant
capability to ameliorate the conditions of asthma. These mice do not
show as much wheezing when they have this bacteria
present in their intestine. Because the intestine is linked
to the rest of the system. Everything starts
here, my mom told me. We’re working in
a new $800 million hospital at the
University of Chicago to try and apply
these same techniques. And we’re uncovering
ecological trends between before the hospital
was operational as a hospital– in blue over here– and
then after the hospital is operational. These are [? flora ?]
patients samples from all across this environment. And we see a
significant alteration of that relationship. And that changes the
way we view hospitals. I’m not going to go into
that right now because she’s indicating to me. We’re putting microbes
in your medical records. We’re actually actively
encouraging people to collect their microbiomes. And we’re developing, at
the University of Chicago and Argonne, sensors
which actually help us to track
people in real time, and help them track themselves. And americangut and britishgut
for me– it says British, it should say English, damn. Anyway, americangut
was developed by us as a crowdfunding routine
with other partners from around the country
to actually actively allow people to have their
microbiome sequenced for $100. And that data goes into
a public repository which is being used by
clinicians and scientists around the world
to contextualize their microbial profile. And utilizing this
sort of information, we’re actually able
to start designing specific, personalized therapies
to treat certain conditions. This kid, he’s a boy. He has crippling food allergies. And so his family came to us. And we sequenced their
microbiome in detail. And we identified bacteria
present in the dad, the mom, and the daughter,
the sister, which were significantly
elevated in those guys and completely
absent in the child. So what we started to do
is take those organisms, culture them up, and put them
into a personalized probiotic from the parents, and we’re now
introducing them into the son. And so far, this
son’s food allergies have been significant
ameliorated. So we are trying to
use this information to develop these
personalized therapies. And I’ll stop there. No. [APPLAUSE] Thank you. And I will be happy
to take questions. Thank you, Dr. Jack. Does this mean that
Genesis has it wrong? And on the sixth
day God created man. And on the seventh he rested. No, he created microbes. Yeah he did. I wish bacteria were
present in the Bible. It would make everything so
much easier to deal with. But somehow in
the almighty hand, he forgot to mention anything– They were there. The meek shall
inherit the earth. They shall. The meek, the
bacteria are the meek. That’s awesome. They are. They’re the smallest organisms. They’re actually– if you take
all the bacteria and viruses in the ocean, they
weigh about the same as 178,000 blue whales. So I mean, it’s a lot
of biomass out there. They’re the most
abundant thing on earth. Yes. So the conventional
wisdom used to be that asthma was
mostly overrepresented in children in urban poverty– Yeah. –because their environment
was so dirty and [INAUDIBLE]. But that doesn’t
seem to [INAUDIBLE]. It doesn’t fit within–
it’s way more complex. I mean, we definitely
do see an elevated level of asthma recruitment in
populations where children are close to roads
or large areas where you get a lot of
particular matter in the air. Do you want to comment on that? With regard to asthma,
there’s also evidence that in populations that
have moved from rural to urban areas, that reduced
exposures to, for example, parasites– Yes. –as correlated to that. Absolutely. And you know, when
I say to people that if you brought
a dog into your home with your newborn child,
that would potentially reduce the amount of asthma,
they panic about that as well. Because conventional
wisdom says dogs actually induce asthma attacks, and
induce wheezing from their fur and from their skin cells. And this is probably because
those children are already inappropriately set up. This is very important. So we are actually trying
to develop techniques to introduce the right kinds
of bacteria back into children. Again that– you,
Chicago, and the MBL– to try and find out which
bacteria they’re missing and then introduce them back in. People– there’s a
couple of papers recently that are showing you just
meet four organisms– in a small cohort of
people, four organisms will protect you against
the development of asthma. It’s a bit more complicated
in that, though. [INAUDIBLE] Yeah, we just don’t know. We’ve actually looked
into this problem. Because when we speak
to the FDA about this, they want to know that
dose-dependent response for the treatment. And we don’t– we’re looking
into those problems for every single condition we deal with. Mine has to do with whether
we incorporate parts of the genomes, or whatever of
bacteria, or whether it’s them acting on their own. It’s rare that we are
actually accumulating bacterial genomic DNA
into our own genome. It’s then usually
acting on their own. I’ll let these guys do it. Because otherwise, I
get like favoritism. Yeah, this may have
already been asked. But I guess my question is,
if I have the right bacteria inside of me, does that mean
I can eat whatever I want? No. Or, or, or, I just don’t want
to eat more than I really need. Well again, your body’s
an ecosystem, right? So there’s a couple of examples
I’ll just go over very quickly. One, when Liping started
eating hamburgers again. You know, we got rid of
his enterobacter cloacea, when he started eating
hamburgers again– as an experiment, I’m
sure, as an experiment– his enterobacter
cloacea came back. That B29 strain
reappeared in his gut. It was probably there in a
very, very low abundance. And then when the ecosystem
changed, it came back. He started putting
on more weight. I actually lost 40 pounds
myself by changing my diet. I was 205 pounds. I went down to 165
by changing my diet to alter my
microbial transition, and my microbial
clocks inside my guts, based on the research
I showed there. And I lost that in 12
weeks, very rapidly. Now I’ve got a bit more lazy
and slack with the kind of diet I apply, and when
I’m eating my food, and my weight started
to slowly creep up. So no, there’s no winning size
solution, one size fits all. You have to be sensible. You have to do exactly
what your mother said, eat a big breakfast, eat
healthy, eat your greens, and you’ll be fine. It sucks, but. [LAUGHTER] Hi, thank you. Can you explain
this slide, please? Does it mean that environmental
simplification is increasing allergies and asthma? And what are the
implications of that? That’s exactly well I’m
inferring with this slide. Although be it a
cartoon fashion, and I’m not entirely
sure I’d suffer peer review angst over it. But the basic premonition is
if you can take your children, and you can expose them to a
more rich microbial diversity, below a certain age. Above a certain age,
we’re not entirely sure it makes a lot of difference. But when their immune
system is developing, especially when their
neurological pathways are developing, we actually
see a significant ability to augment their physiological
state by increasing their microbial exposure. Now there are very,
very few studies where we’ve done
that in children. We just published one
with cow’s milk allergy. When we got them as
infants below six months, we were able to ameliorate
cow’s milk allergy in all the infants we treated
by adding the right kinds of bacteria back in. We published that
a few weeks ago. But it’s very few instances
we’ve done it in humans. Animal models, it’s very robust. If we get the mice when
the mice are infants, and we have the
bacteria in, they are protected from
the later development of those conditions. If you add the bacteria
in after they’re infants, when they’ve started to
mature, you get no protection. So I’m interested in
your work on autism. Yeah, I didn’t
cover that as much. And I wanted to, but
they cut my time. It’s your fault. [LAUGHTER] Well can you address
that a little bit now? Absolutely. I mean, you know–
I think that– I have a child with autism. So do I. I know that. I [INAUDIBLE] from reading. So I think that given that
we don’t really know what the cause is of autism today. I understand a bit
what you covered in how bacteria can affect autism. Yeah. Are you saying that it can,
similar to your discussion of asthma, ameliorate
the effects of autism? Do you think that there
is a strong linkage between the neurological
development, or the sort of clustering
of neurons and our gut– Yes, I mean– Or none of the above? No, no both of the above. But let me tackle one point. Yes. Neurological diversity
in our community is incredibly important. I don’t actually want to cure
my son’s autism because he’s wonderful just the way he is. And it’s not crippling
his life, you know. But there are children
who are locked in. And they have significant
problems actually dealing with life because
of their autism. And autism is a spectrum. So there’s not, again, no
one size fits all solution. But what we have shown is that
the disruption of bacteria in the gut can cause
your gut lining to become much more leaky, right? This leaky gut syndrome that
we hear about a lot nowadays. And that allows more
metabolites to pass through– pass across the
gut membrane into the serum. And some of those
metabolites have been shown to increase
permeability in the blood brain barrier leading to an alteration
in neurological chemistry. If that’s happening very
early in life, as we just said with the development
of those neurons, it could be leading to changes
in neurological connections, and even the
myelination ratio we see on the nerve
endings in the brain and in the central
nervous system. That’s the fatty tissue
around the nerve. And that is potentially the
target we’re going after. We don’t have absolute
evidence of that right now. But that’s a– a lot of
evidence to suggest that we are in the right ballpark. The Brain Initiative that
the White House launched– and we have a
Microbiome Initiative being launched in January– but
the Brain Initiative actually significantly helps
us in this space. Because it allowed
us to recruit people through Argonne, and
you, Chicago, who are helping to develop on
our neurological program, and allowing us to
visualize those neurons and model them in computers
so we can see what impact this disruption in
the microbial flora has upon that development. And it could be not
just in the brain, but also in the nerve
endings inside your gut. Your entire nervous system
is it really important. But, anyway. We have time for one more
question, right in the back. I like this. More, more. With your mouse studies
originally on obesity, is there any sense
of age dependence in terms of when that can
be induced or reversed. For obesity, I’m not
aware if that’s actually being looked at. I mean– so in the
studies– and we were talking about this
earlier– in the studies where antibiotics have been
used to disrupt microflora, yes, happening very
early in the development of the animal actually leads
to the obese phenotype. Later, if you take antibiotics
as a juvenile or adolescent mouse, it doesn’t lead to
an induction of obesity. In the microbiome bounced
back quite rapidly after that. In humans, we just haven’t
done enough trials because it’s ethically very
difficult to just give lots of children antibiotics
and the other ones not. [LAUGHTER] But theoretically, the same
premise should be true. Now– yeah, age could
be a significant factor. More questions. Yeah. Jack, I just want
to take the liberty to ask you to comment a little
bit about– you referenced your partnership with MBL,
can you talk a little bit about the new experiences
and opportunities that partnership is
bringing to students? Yes, where’s my card? Just because it’s in the
backyard, here, for everyone. And we didn’t get enough time. But I think people would
be interested to know how the students are benefiting. Yeah, we’ve developed a really
exciting graduate program, a boot camp like we were in
the army, when we literally take everybody down there and
we trap them in Woods Hall. Which is an awesome
place to be trapped, it’s got beaches and everything. And we basically hammer
them with knowledge as much as we possibly can. And a lot of my
graduate students are now taking advantage
of that boot camp to learn everything from
neurological pathways, to statistics, to microbiology,
to molecular engineering at the base level. So they actually start
out their graduate career with this really exciting
multi-disciplinary factor. And the undergraduates are
taking advantage of it as well. We have a lot of undergraduate
training programs out there. And I’m taking advantage of it. Because it’s actually an
excellent year-round research program at the MBL. And even though I
don’t necessarily want to travel
there in the winter, in the summer’s
more awesome, I’m still actually
actively collaborating with my colleagues out there
and taking the resources that we have out there
and utilizing them. They have one of the world’s
best marine resources centers that you can find. That’s why it’s one
of the world’s best. I’m losing my
sense of a purpose. But the MRC actually helps us. And we started working
on an immune model in an innate organism
called ciona, which is a tunicates little
thing that sticks onto rocks. And when we challenged
this thing with bacteria that it got theoretically
from its mother, it seems to change the
development of the microbiome. So we are actually
utilizing ciona as a model for microbial
development in children in relationship
to the work we’re doing in children already. And trying to manage
that system, that animal model, a new animal
model, in a way that helps us to understand
how this works in people. So the MBL has been a
phenomenally useful, if you’re willing to
take advantage of it, resource that faculty members
and students can take advantage of. Yeah, is that good? Yeah. Yeah, I didn’t
read from my cards. Thank you. [APPLAUSE] So, my name’s Shalin Desai. I graduated from
the College in 2005. And this year I’m
taking over as president of the Alumni club of Boston. So of course I’m
going to show you guys what you guys should
do to get more engaged. First of all, I want to thank
you guys for showing up. It’s awesome that
you guys come out. It’s awesome to engage
with the University. And I couldn’t think of a more
informative or entertaining way to do so. And I also want to thank our
Alumni Board of Governors and the Alumni Club of
Boston Leadership Team. This year, we have
a brand new team. It’s 15 people strong. So it basically multiplied
three-fold over last year. Some of those guys
are here tonight. So if you guys could
stand and be recognized. These are people
that you should be talking to you if you
want to get more involved with the club. We’d love to see
you more at events. So the Harper isn’t
the only thing that we do we do a lot more. And since we’re a
volunteer-led club, we can make it into
anything that we want. So your input is crucial. We’d love to get
you guys engaged. We’d love to get you
guys participating. So if you like to know
more about Harper Lectures, the alumni travel program, or
any of the other University events that we host here
or around the country, please talk to one
of us, stop by, say hello, talk to
one of our staff that’s here from the
Alumni Association, or come up to the
registration table. A couple of us will be out there
and we’re happy to talk to you. So at the beginning
of the lecture, Tracey mentioned that we have a
125,000 person engagement goal. And just by being
here tonight, you guys are actually partici–
engaging in that, helping us meet that total. So I want to encourage you guys
to keep showing up and joining thousands of alumni
around the world, and giving support to
things like scholarships, you saw a couple of students
in the video earlier today, new inquiry, attending events,
coming up with events, so if you’ve got some
ideas, please talk to me, or leading reunions,
and so much more. So a couple of things that
I want to shell out to you guys that we’re doing over
the next couple of months. We’re doing fun stuff,
educational stuff. On November 4,
there’s a wine tasting at Urban Grape, that’s
in the South End. We’re doing our career
month on November 18. So if you are going through
a career transition, or if you want to polish
up on your skills, or if you want to network
with other alumni in the area, I definitely encourage
you guys to do so. It’s at the Omni Parker House. There’s a new flux exhibit
at the Museum of Fine Art. And it’s actually curated
by somebody who graduated from the University of Chicago. She’s a Senior
Curator at the MFA. And she’s actually going
to be leading the tour, so we get the inside
of the inside scoop of what’s going on there. And if you’re planning
really far ahead, in January, we’re actually to be talking to
the assistant general manager of the Celtics. And he’s an MBA from the
University of Chicago. He’s an undergrad. Oh, He’s an– Econometrics undergrad. He deals with numbers. I wrote papers. I don’t know. So he’s going to be meeting
us at the TD garden. And he’ll talk to us and we’ll
watch a Celtics game together. So all these things you can
find out on our specific website uchicagoboston.org. If you guys are in the area, if
you have the physical address in Boston, and it’s
not updated with us, please make sure that
you update it so you get all of our e-mails. We have a Facebook page. All you have to do is Google
U Chicago Boston Facebook. You’ll find us. Soon we’re going to have
an Instagram account so we can just embarrass
you guys by taking pictures at events and posting them. So all these things
are happening. It’s a really exciting year. We’re here to make it happen. And we hope that
you guys will too. So, thanks for coming out. [APPLAUSE]

Leave a Reply

Your email address will not be published. Required fields are marked *