My name is Woody Hastings and I am a research professor
of Molecular and Cellular Biology at Harvard University in Cambridge
and I want to tell a remarkable story
about the discovery of quorum sensing.
How it came from our experiments in which
we discovered what we call autoinduction
its a more proper word perhaps
but quorum sensing also describes it.
Now I wasn't completely concerned about it
with no objective no idea
it would ever lead to anything important
lead to anything it was just a question
why do cells grow exponentially
and have certain processes
bioluminescence for one that don't turn on for 3 hours
then turn on very very fast so it was a basic question
and really this is what basic research is,
is seeing phenomena I said Georgie you had seen
what many people have seen and
think what no one else has thought
is idea of discovery it is also called non-directive research
it means no one else directs it
doesn't mean you don't direct it,
you better direct it and we directed our efforts at
trying to understand why these bacteria
didn't for many hours turn on their genes.
It starts really about 10 years ago in my laboratory.
I saw graphs like this
in which the cells grew exponentially
note on the ordinate that the
scale is logarithmic whereas bioluminescence
for the first 3 hours didn't rise at all
well I didn't I was trying to find
someone when I got phone call from
a graduate student at the University of Chicago
his name was Kenneth Nealson and
he said I am doing the genetics
of bioluminescence in bacteria
and I am having trouble in getting
cells to produce luciferase.
I said I have never thought of this experiment,
luciferase wouldn't always be there.
I urged him to enroll in the physiology course
at the Marine Biological Laboratory in Woods Hole
and we would use his spare time in the course
which is nonexistent of course to study this phenomena
which I was so concerned about
and this graph illustrates
the phenomena which Nealson
came to study with me and
he concluded that in fact
the first 3 hours there was no synthesis
of messenger RNA there was no synthesis
of luciferase protein and there
was no activity of luciferase.
Many alternatives to that possibility
you had to we had to show that was true
and we concluded that in fact the first
3 hours was a time in which the cells
were producing a substance which
was then responsible for the synthesis
of messenger RNA for luciferase
that substance was an inducer
and we said this is autoinduction its doing
it all by itself you don't have to add
anything to get any cells
and we took medium after cells removed
the cells and we had medium that had been used
for growing a batch of cells
and we showed that we could isolate
from that media a substance that would
cause cells at low density to emit light.
Well that was confirmed beautifully
by Abrhard and Nealson
in later experiments. Abrhard a decade
following our publication of the
original paper was able to work out
the structure of the autoinducer
to be homoserine lactone shown here
and to show that in fact different
chain lengths were used by specific bacteria
to act as autoinducers
and they would not respond.
Peter Greenberg became involved in this
and showed that very importantly that cells
could communicate with other species
by different chain lengths
of homoserine lactone like this.
So having this molecule identified
he went on to synthesis it and made it
available to Ken Nealson who with his group was
able to do the definitive experiment
to show what we had shown with spent medium
he showed with pure synthesized autoinducer
and here is the way he did it
It’s a funny graph and you have to study it a little bit
but he put it in a chemostat to cause cells
to be fixed in a certain cell density
and as the cells got down to a certain
cell density their biolumenicesece just turned off
and then at that point they get
the cell density at this level they get the
useful concentration and then added autoinducer
they added no more glycero. The cells responded
by immediately synthesizing luciferase
even though they were very few in number.
There is no quarrel there I can assure you.
This summarizes what I think the
fact that the phenomena was established
by 1980 you were very clearly that
bioluminescent bacteria luciferase
was stimulated by virtue of a substance
in the media produced by the cells themselves.
Many people did not agree
with this conclusion.
They thought it was some quirky phenomenon
associated with luminescent bacteria
and didn't apply to bacteriology
in general to bacteria in general.
By 1990 as outlined in Bonnie Bassler's
beautiful expose in this series
this turned out
she and others showed that genes responsible
for this phenomena were present in all kinds
of bacteria and they are especially important in disease bacteria
for the production of toxic substances
was regulated by autoinduction
But how did the name quorum sensing
displace autoinduction for this phenomenon.
It is described by Pete Greenberg
as occurring at a dinner where he
and several colleague were discussing the
phenomena with other non-scientists
and one of the non-scientists
who happened to be a lawyer of course
said ahah that phenomena
is really a quorum sensing
only when the bacteria get to a
certain level in culture,
when there is enough autoinducer
produced to cause the phenomena
we will just call it quorum sensing
and he introduced the term
Greenberg did and from then on its history.
It has turned out to be extraordinarily
important in many different disease states
biofilms utilize autoinduction toxic cells noxious species.
The toxin is regulated by
autoinduction like quorum sensing.
Only when a quorum of cells that
is a lot of cells have infected the
body of the organism you let’s say the cells produce
the toxin and cause damage and they really cause damage
at this point if they produce a small
amount of the toxin with time,
that would in fact defeat the purpose
because the organism would if you will
in some sense or in some way sense
the presence of these bacteria
and raise defense against it.
This illustrates that basic research
can lead to phenomena and does lead to phenomena.
This is only one of many examples
that will lead to results that will have very very
important applications such as autoinduction does. Thank you very much.