okay good morning everyone welcome to i
sir and kudos to the team for putting
this event together let me get straight
to it
I am a biologist by profession and
that's what I'm going to talk to you
about today but before I start talking
to you about biology let me confess that
biologists love labels right we love
complicated names we come up with all
sorts of complicated terms to describe
best little sub-discipline of biology
that we all study right
but biologists essentially irrespective
of what label he or she is hiding behind
is essentially interested in studying
one thing right trying to understand
life we all want to know what it means
for it for an organism to be living what
allows this organism to continue to live
what life used to be like in the past
what it's like today and what it's
likely to be in the future right and
like all fundamental things life is
incredibly hard to define but it's very
easy to describe and so that's the route
that we typically take we like to
describe life we like to understand it
by looking at its properties right and
one of the most ironically unchanging
properties of life is its ability to
keep changing right so what life does
all the time is exist in a state of
dynamism constant flux everything is
always changing and what's amazing about
these changes is that is that they're
occurring at all levels of organization
right so they're occurring at the level
of proteins moving around inside the
cells of your body performing various
functions they're working at the levels
of cells constantly pulling and pushing
stuff in and out of them to ensure that
they work the way they're supposed to
these changes are constantly occurring
at the level of tissues cells coming
together to form structures that perform
specific functions which are constantly
being remodeled in your body and they're
also occurring at the level of the
organism you as an individual are also
constantly changing you're responding to
the environment both internal and
external and you are modifying your
behavior your metabolism your physiology
to suit a particular kind of environment
right these kinds of changes are also
constantly occurring at the level of
communities which means organisms coming
together to perform collective
activities the TEDx eyes
boon event for example is a community
which is a dynamic community right
people are going to come people are
going to leave people are going to come
and talk people are going to sit and be
part of the audience and so all
biological entities are constantly in
this state of flux
so what biologists really spend all of
their time doing is trying to understand
how living systems maintain this
dynamism right and how do they regulate
this dynamic because you can't let
things run unregulated
in a living organism but as you can
imagine change of any kind particularly
change that occurs with respect to time
is incredibly hard to pin down simply
because it's constantly changing right
and so you know to just give you an idea
of the kind of complexity that one is
dealing with changes like this proteins
you know flopping around in a Cell are
occurring over time frames prime frames
of about nanoseconds right whereas let's
say humans evolving from apes is
something that took millions of years to
occur right so a biologist is not only
trying to capture change at these
multiple levels of organization but is
also dealing with these vastly different
time frames right nanoseconds to
millions of years okay and you know the
the the bane of looking at change in
biology is that when presented with
something biological a biologist must
look at it in the context of the changes
that this entity has been through for
example if I were to show you a flower
it would be really easy to describe this
flower in its current state right its
shape its size its color so on and so
forth but a biologist must look at this
flower and try to imagine what this
flower will be once it's fertilized it's
going to turn into a fruit right this
flower also used to be a mass of cells
that look nothing like a flower and
could in principle have given rise to
pretty much any organ in a plant right
this flower evolutionarily speaking
wasn't a flower at all it was just a
group of cells that performed some
completely different function which have
been shaped into its current form to
serve a certain kind of property or a
function that this organ of the plant is
supposed to play and so a biologist
really can never dissociate from this
constant change that biological systems
are you know undergoing and of course in
addition to this slightly academic
question of you know understanding life
understanding change in biological
systems also has its advantages in
improving human health for example an
oncologist trying to describe trying to
prescribe treatment for a tumor will
need to know what this tumor is going to
look like over the next year if left
untreated right where this tumor came
from you know what it used to look like
how fast it got to the point where it's
gotten now so that the treatment regimen
that's just--that's that that is
prescribed can be most effective and so
so essentially understanding changes in
biology have academic value and of
course also in improving you know our
day to day lives right so having
established that change is the only
constant in biology how does a biologist
then capture change how does the
biologists try to understand change well
we do it much in the same way that a
filmmaker for example tries to capture
motion right we essentially just take
snapshots right and if you take enough
snapshots you should have a fairly
complete image a fairly complete picture
of the biological entity that you're
trying to study
these snapshots could be photographs
taken like this through a microscope or
even without a microscope or could be
something slightly more esoteric for
example the levels of a particular
protein let's say in your bloodstream or
the levels of a particular protein in a
cell they could also be things like the
sequence of the DNA that make up your
chromosomes and how that changes over
time
or it could be the number of organisms
of a particular kind in let's say a lake
or a forest right tracked over time and
so these snapshots depending on what the
kind of question is that is being asked
can be of a variety of kinds but
essentially they're snapshots right and
they need to be strung together over
time to make sense of the biological
system as such great so having laid that
foundation for biology in general let me
tell you a little bit about what I do so
I have a laboratory here at ISO Pune and
I am essentially a microbiologist which
means that I study bacteria well I study
primarily bacteria
and what I am really interested to know
is how bacteria undergo transformation
from being antibiotic susceptible or
antibiotic sensitive to antibiotic
resistant right now several of you will
know that anti by antibiotic resistance
or an antimicrobial resistance is a
burning biomedical problem today
you know infectious agents that were
that we could tackle about 10 or 20
years ago very easily with antibiotics
today we simply can't because several of
those antibiotics have stopped working
against these bacteria right I'm trying
to understand how bacteria undergo this
transformation is therefore potentially
going to help us to slow this
transformation down right so how do
bacteria go from being drug sensitive to
drug resistant well turns out that this
process is essentially akin to what one
calls Darwinian evolution right where a
population of bacteria which are drug
sensitive to begin with sensitive to the
antibiotic to begin with when exposed to
the antibiotic eventually become drug
resistant right and the way they do this
is by essentially just enrichment of
pre-existing variants in any population
that are able to withstand the drug
better so the more drug a population of
bacteria will experience the greater the
chance that they will become resistant
simply because they've experienced that
much more drug right and in that sense
India's at the epicenter of the AMR
crisis of the antimicrobial resistance
crisis and part of the reason for this
is because of the just the quantum of
antibiotics that get consumed in this
country right not only are we consuming
a lot of antibiotics in India but we're
also using them fairly loosely right so
the regulatory guidelines aren't as
stringent as they should be and what
this means is that we're essentially
exposing bacteria pretty much anywhere
you can think of two antibiotics which
raises the chance that they will
eventually evolve to become
drug-resistant right so what do we do
about this in the lab well we do
something called laboratory evolution
right essentially simulating this
process of transformation from drug
sensitive to drug resistant in the
laboratory so that you can study all of
its bells and whistles figure out how
various things come together to lead to
this change in phenotype of bacteria and
then hopefully come up with a way of
slowing this process now so how do we do
this very simple we start with a whole
lot of cultures of drug sensitive
bacteria bacteria that will be killed by
the antibiotic right and then over time
because time is the only constant that
we have in under our control
we we expose these bacteria to various
kinds of antibiotics in various
different ways to be able to mimic all
of the different niches where bacteria
may encounter antibiotics right and
these are incredibly variant these are
incredibly variable as I'll tell you in
the next slide and we continue to do
this until these populations that we
started off with which remember were
drug sensitive have become drug
resistant right now what we do is a
little bit of detective work
we essentially trace back how this
process occurred and you know one can
ask all sorts of interesting questions
was there a single step process was it a
single step that took the bacterium from
drug sensitive to drug resistant where
they multi multiple steps involved right
how do changes in genes how two changes
in the sequence of the DNA that makes up
the the genetic material of these
bacteria how does that correlate with
this change in drug sensitivity to drug
resistance one can also ask how
environmental factors you know factors
other than drugs contribute to this
process right and finally of course are
there ways in which by which we can slow
this process down and that's really the
the final goal of all of these endeavors
to give you a quick quick example of the
kind of information that one can get
from these kinds of experiments right
this was a study that we did last year
well we did over the last couple of
years was published last year where we
essentially tested how drug pressures
right low versus high drug pressures
influenced this evolutionary trajectory
going from drug sensitive to drug
resistant so what do I mean by low end
drug high pressures well high drug
pressures are typically high drug
concentrations concentrations that are
therapeutic that are used to kill
bacteria these are the kinds of
concentrations that bacteria would
experience let's say in your body when
you're consuming the antibiotic as tree
went right on the other hand low drug
pressures usually are you know are
produced when drug concentrations are
much lower than the lethal concentration
of the drug or when drug exposure isn't
continuous right and these kinds of
environments bacteria will face in you
know natural reservoirs for example soil
in water where there's antibiotic
contamination right or even in your body
when you stop consuming antibiotics
before the course is supposed to have
been completed right and drug
concentrations paper off so we were
essentially asking how these two kinds
of conditions change this transformation
from drug sensitive to drug resistant
and what we found was pretty remarkable
turns out that when you have very high
drug pressures drug resistance does
evolve but it evolves as a single step
leading to a very heterogeneous mixture
of bacteria which are resistant to
either high intermediate or lower levels
of antibiotics so you have all sorts of
resistant mutants that you can add in
that you can isolate when you have low
drug pressures however it turns out that
this process is not a single step
process right it's a multiple step
process involving these intermediates
which we call drug-tolerant bacteria
which actually are only good at handling
low concentrations of drugs that the
concentration that they were facing you
know when they were undergoing this
process of transformation but what's
what's really scary about these
intermediates is that when they do
evolve drug resistance they actually
only River evolved resistance to
extremely high concentrations of drug
which essentially means that imagine a
bacterium that's swimming around in a
you know in a water body facing
extremely low concentrations of
antibiotic it's likely that this
bacterium is going to evolve extremely
high involved resistance to extremely
high concentrations of the drug without
ever having seen those high
concentrations of the drug and so if you
are infected by one of these bacteria
chances are that this antibiotic is
simply not going to work as a
therapeutic anymore right and so so what
this really you know leads us to is a
strong advocacy for what one calls
antibiotic stewardship right
we simply cannot be consuming the kinds
of antibiotics that we are in all of
various ways that we are because
antibiotics are everywhere at various
levels and various concentrations and
you know we may inadvertently actually
be selecting for drug-resistant bacteria
outside the human body you know in the
soil in the water that we're drinking in
all sorts of places right anyway all
right so so let me let me quickly wrap
up and summarize what I have told you
today so I've tried to convince you that
biology is essentially an obsession with
change right we love looking at how
biological systems are constantly
changing constantly dynamic and
understanding this dynamic this dynamism
of biological systems is part of
understanding what it means for life to
be called life right these changes are
inevitable and they're necessary because
biological systems must constantly
change in order to adapt to the various
environments that they're challenged by
what I've told you through a snippet of
my work is that the path that biological
systems take to change is just as
important as the as the endpoint right
we need to we need to understand how
these changes occur rather than just
what that change is right and finally
one can very easily if one puts one's
mind to it linked micro and macro level
changes in biology together right change
is occurring at the molecular levels
changes occurring at the cellular levels
at the organismal level and so on and so
forth and a complete picture of life of
biology is only possible if we put all
of these together I just want to leave
you with a thought which is that you
know human beings are also part of
biology right and so the same forces
that are constantly changing all other
biological entities are also constantly
changing us right and so if we are going
to understand ourselves we need to take
this into account and we need to be
cognizant of all the diversity and
plurality that these biological forces
of change are generating in human beings
as well thank you so much
you