Fighting Brain Tumors and Alzheimers | Robert Harris
‘I need to know’ – that’s what drives me. I am inquisitive and I like to be able to think, to be innovative in my thinking and a lot what we do doesn’t work.” ― Robert …
My name is Bob Harris. I am a professor of immune therapy
within neurological diseases
at the Karolinska Institute in Stockholm, Sweden.
What is your main research topic?
My main research topic is really to understand
we do this in a variety of settings.
Primarily it’s been or historically it’s been
within the field of autoimmunity
where we focus on multiple sclerosis
but in recent years we've also expanded into
Alzheimer disease and brain tumors.
So, inflammatory diseases
of the central nervous system
and what we're interested in doing is learning
how the diseases arise,
how they are perpetuated
and what can we do to stop those processes.
So they're designing novel types of therapy to try and
reduce the disease burden or hopefully to even stop it.
What are actually neuroimmunological diseases?
Autoimmune diseases at least are
diseases in which the body attacks itself.
Usually, your immune system is designed to respond to danger,
to things that are coming from outside like infections,
but sometimes for reasons we don’t understand why
then the body turns on itself
and starts to destroy its own tissues
and these are called autoimmune diseases.
What happens in chronic inflammatory diseases
is that there is disregulation of the regulation
and that means that the immune system
starts to do things which it shouldn’t do.
So, if you have something that goes wrong in your body,
then your body should respond and
take away whatever it is that is not right.
And then that can be either something
that happens to your own cells
when they become abnormal in the form of cancer
or it could be that you get infected by
by something, a bacteria that comes
into your body that shouldn’t be there.
So your immune system is there to protect you
from these things but sometimes
it loses the instructions not to
respond to itself and so it starts to attack itself.
There are many reasons
for this occurring,
but really your immune system becomes
diseducated and starts behaving in a bad way.
And then, when it starts to do that,
it starts to attack itself
and it can lead to dysfunction
in your body and depending on where
the damage is done
then you can either then develop diseases of
your brain, your liver, your pancreas or your joints.
What is your approach to try to find a balance again?
The first thing to try to readjust the balances
is to actually prove that there is an imbalance.
That’s one of the things that we can do
by studying our animal models
and by studying our patients’ samples
to actually try and work out what’s happening
in the blood of these individuals who actually are sick
and how do they differ from people who are not sick
and that would give us some clues about
the immunological processes which are occurring
and that would then give us clues about how we can stop them.
What is your special approach in your lab or what is your idea?
We have a number of approaches
to try affect immune therapy.
The major focus in the last five years
has been on novel cell therapy.
One of the immune cells which are involved in
these chronic inflammatory conditions
is the cell called a Macrophage
and these are very numerous,
they are all over your body in all your tissues.
and you have a number of them
immature called monocytes circulating in your blood
ready for action in case something happens.
So when you get an infection in your skin,
then there will be a recruitment of these
monocytes to repair that part of the skin,
that'll go from the blood into the tissue,
become macrophages and do what
they are supposed to do to kill the infection.
The resident cells which are all over the body
have another role and we think that
that’s mostly to keep things in check,
the homeostatic functions, to keep the balance.
So, there’s an interplay between these two cell types.
Then the macrophages themselves can have different properties.
They can be nasty ones that chew up the bacteria,
these are pro-inflammatory,
and then there are others which
calm things down and they have anti-inflammatory function
and there should be a balance between these two.
It’s like Yin and Yan,
so when you activate one side,
then you should have the other side that comes and regulates it.
So, in chronic inflammatory conditions
like multiple sclerosis then you have an over
activity of these pro-inflammatory cells
that rip your brain tissues apart and that’s why you get the disease.
So, our hypothesis is that you have
an imbalance in these two populations.
People who get these chronic inflammatory
conditions are a little bit trigger happy
with the pro-inflammatory side
and maybe they are actually insufficient in
down-regulatory side, the anti-inflammatory side.
In settings of cancer, for example
in brain tumors, then it’s the opposite.
The tumor is actually is able to survive
because it’s anti-inflammatory.
So in this case, then it’s the other side
that’s actually a little bit too active and
you are lacking the pro-inflammatory side.
So, in each case, in each scenario
then our hypotheses is that if you give back
cells of the right sort,
so in autoimmune conditions – anti-inflammatory,
in cancer setting – pro-inflammatory cells.
So, we can take blood from a patient,
we can purify these monocytes,
make them into macrophages,
stimulate them to be pro-inflammatory or anti-inflammatory
and inject them right back into the same patient.
Hopefully, at the site of where the disease is
and that would then restore the balance locally
and then it should halt the disease process.
What is the peculiarity of your research?
One of the peculiarities of our research is
is that not many people work with these cells,
these macrophages that we are working with.
They are sort of considered to be the garbage collectors
in the rest of the body, when you have some damage or
you need to get rid of something, you get infections,
some bacteria in the skin they get taken care of,
the macrophages are the garbage collectors.
They come up and get rid of all the dead tissue
and make things right again.
This is why you have macrophages in
every organ in your body
As well as theses circulating ones that
they can come in high numbers if you really, really need them.
They are like soldiers that are pulled onto
the battlefield as extra resources,
but many people don’t think then that
these cells are so smart, but they are very numerous.
So we actually think that they are a little bit underestimated
and very few people have been working with macrophages
until the last five years and then it's been sort of a renaissance in the field
and the abilities of these cells to be multifunctional
more than just the garbage collectors
have actually become a little bit more apparent.
So now there’s a lot of interest actually in what they do,
but people are still not really interested
in these being able to use them
in immunotherapy the way that we are.
It starts to be tested. People have actually
started to use our protocol.
One of the papers we published where
we could show that we could induce
anti-inflammatory cells in human cells
which we published in the Scandinavian Journal of Immunology.
It’s been the most downloaded paper
in the last couple of years.
So there’s a lot of interest and
some people are actually starting to report
using our protocol in their systems and
in other disease models that we haven’t studied ourselves
and it still works as well. So
I think it's coming and it's not
going to become so peculiar but
they're not so many people who think this is
the first cell type to study
and that's why we are a little bit strange.
Why do you think your approach is better than others?
It’s not a question whether it’s better,
it’s a question of time and money and efficacy.
One of the beauties of our theory is that
the hypothesis that we will use
patient’s own cells.
So that there won’t be any problem with any rejection
when we try to put these back in to the same person.
They are their own cells they are just not doing
what they should do.
So we giving them a little bit of
help along the way to actually turn into the cells
that are doing the things the right way
they should do and put them back in
and I think that’s a smart approach.
I think that what we have seen from other immune therapy approaches
are that even if they are very successful and if we
take an example of Rheumatoid Arthritis where
one identified the molecule called TNF which is one of the
sickening components which is
very, very highly expressed in Rheumatoid Arthritis patients.
So, they found ways to inhibit this molecule
by using antibodies or soluble receptors which then can take it away.
The immune system has been developed for hundreds of thousands of years
and suddenly you take a part of it away.
It's a bit like chopping your foot off
you would be still able to walk, you would be able to hobble along,
but you won’t be able to run and
you won’t be able to climb stairs in a good way.
It doesn’t really make sense to take something away.
So I think that our approach is just
giving back something that is really a little bit insufficient
is a more natural way to actually reset the balance.
The next thing with this is really to go into patients.
One of the challenges
is trying to go from experimental systems to humans
is me not being a medical doctor is
that I'd then have to engage clinicians.
So at the moment I need to try and
get funding to fund this
and then try to find
doctors that are willing to try it and
that’s really where I want to go.
If I can make life better
by just one patient then I will feel that
I’ve done my job as a researcher.
How much do we actually know about
ourselves or about our body functions?
We now know a lot about the body functions and we've learnt
tremendous amount about the immune system, but unfortunately
one of the challenges I see is that we have always been studying
disease, we have studied with allergy,
we study people with autoimmune disease, we study people with cancer,
but we don’t actually know too much about healthy people.
We study aging even as well, but
this is when things start to go wrong. But we actually have
relatively little experience of healthy people
to actually know what’s going on in healthy people
and how does their immune system actually look.
Is it always non-activated or
is it always on the go a little bit?
How’s the regulation done there?
So, I think that we need to actually study health
in order to get a better handle on
what goes wrong when you get a disease.
But we know a lot and there are very many
therapists that work very well and lots of
new therapies being developed so
the knowledge that we have it's actually made tremendous progress.
What do you look forward to now?
What do I look forward to? Summer holiday.
No, what I look forward to in research is actually
the research community as a global community
and a lot of smarter people out there,
lots of smarter people than I am
and what’s nice is that we then share this knowledge and
what I look forward is actually a major breakthrough.
It’s been a long time since there has been a
major breakthrough in medical research.
Maybe the last really major significant thing
was the small pox vaccination and that’s way back in the 60's.
So it’s about time that we actually came with something
really revolutionary and we've had
really good advances with sequencing the genome and so on,
but most of the advances has been technological.
But I think it would be nice if we actually
could really nail one disease and
eradicate it from the face of the earth.
You got a prize as a great teacher.
What is your role, how do you see yourself as a professor?
You know that some people are good at doing research,
some people are good at writing things, some people are good at talking.
I seem to have a talent as a teacher.
I realized this quite early on
and I am heavily involved in
all sorts of training and development of training.
So it’s something I enjoy doing.
It’s fun to be able to inspire other people
to be better in what they are doing and that’s the point of a teacher.
Whether it's to students to inspire them
in their quest for knowledge
or whether I do a lot of leadership training,
especially for our PhD supervisors
and to inspire them to actually be good in those roles.
What is good research?
That’s a very interesting question.
Beauty is in the eye of the beholder and
so different people would tell it's different things.
I think good research should be based on
sound ethical principles, good critical thinking
and should be interesting.
So that for me is what good research is all about.
Research is all about searching again. That’s where the “re” comes in.
So, often good research is nowadays
is actually going over old research
but using new methodologies
in order to address these questions
and that could be just as exciting as
finding something completely new.
And what is a good researcher?
Ah…good researcher I am not sure,
you need to ask someone else.
No, a good researcher should be somebody that
is really interested in asking questions.
“I need to know” – that’s what drives me.
I am inquisitive and I like to be able to think,
to be innovative in my thinking
and a lot what we do doesn’t work.
So a good researcher needs to actually
have the stamina to face failure because
90% of the time we fail in what we are doing.
We ask questions, we pose hypothesis, we test them
and they show not to be true,
so we have to go back to drawing board and start again.
So I think a good researcher is actually
somebody that doesn’t give up,
that actually sees the big picture
and for me it’s the patience.
If you see people suffering or if you see people dying
from the diseases, all the diseases we are interested
in studying there are no cures for them
and they are horrible diseases that really affect people.
We could have picked up something that would be easier to fix
but that’s not so interesting for me.
I like the challenge of actually doing something
that’s undoable at the moment
and really to make efforts to do that
and I think that’s also the essence of
research, at least in a clinical setting,
that want you to actually be trying to do something
that’s going to be of use to the patients.
Thank you very much, Bob.