February 17, 2025 • 35 mins
Garvan is one of Australia's largest independent medical research institutes with a single focus: to make discoveries that will improve health for all. In this episode, you’ll hear from Executive Director Professor Benjamin Kile on how he came to be at Garvan's helm and his strategy for driving extraordinary science that will have transformational impact for patient lives.
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Episode Transcript
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Dr Viviane Richter (00:01):
On this podcast, we've met more than 25 researchers from Garvan,
each working on the next game changers for cancer, immune
disease and inherited genetic conditions, amongst others. But we've never
sat down for a chat with our leader. Professor Benjamin
Kile is an accomplished molecular biologist, internationally recognised for his
(00:23):
research in blood cell development that informed a major breakthrough
for cancer treatment. Benjamin has a vision for Garvan to
accelerate and empower fundamental biomedical research that will lead to
better prevention, treatment and, ultimately, cures for disease. So, what
does that mean and how will Garvan get there? Welcome
(00:45):
to Medical Minds, the podcast that takes you inside the
labs at the Garvan Institute of Medical Research. I'm your host,
Dr Viviane Richter, and it is a huge pleasure to
have in the studio today Garvan Executive Director, Professor Benjamin Kile. Welcome, Ben.
Professor Benjamin Kile (01:02):
Thank you, Viviane. Wonderful to be here.
Dr Viviane Richter (01:04):
Ben, before we talk about how you came to be
at the helm of one of the biggest medical research
institutes in Australia, I'd love to know how it all
started for you. Did you always know you were gonna
be a scientist?
Professor Benjamin Kile (01:16):
Well, in hindsight, perhaps it was, it was obvious, but
growing up, I don't think it was. I was always
interested in the world. I was always interested in history.
And as a young person, I had a series of passions, obsessions,
I guess you could call them. Uh, when I was,
in primary school, I was fascinated by ancient Egypt, and,
when I realised there were such people as archaeologists, I
(01:38):
was determined to be one. Later in life, I, I
became really, really interested in, in astronomy. I guess, in part,
driven by that wonderful Carl Sagan series, Cosmos, and for many,
many years, wanted to be an astronomer-slash-astronaut. And then, at school,
high school in grade 8, doing biology, I was introduced
(02:00):
to the concept of genes, and that was a really
signal moment in my life, realising that there were things
called genes embedded in your DNA that, uh, regulated the
program of life. And I think from that point on
it was always I was always interested in biology, but
didn't really know where that was leading. I didn't really
know what scientists did. I didn't really know what research was.
(02:22):
So when I went to university in the early 90s,
I ended up doing a combination science and law degree.
With the words of my parents ringing in my ears,
I was keeping my options open. I didn't really know
where my career was headed. And it was towards the
end of my, my two degrees that I experienced, I guess,
the first loss of someone close to me who, who
(02:43):
wasn't a grandparent, whose death really seemed to interrupt the
natural order of things. And that was my uncle, um,
who was one of the sort of formative people in
my life. He was an extraordinary character, larger than life, and, um,
full of energy and art and politics, and just a,
a real inspiration to me. And in 1994, he died
of AIDS, and that was shocking. And it wasn't a
(03:06):
light bulb moment in the sense that it, it signaled
to me what I needed to do with my life,
but I guess over the years that followed, I started
to wonder whether I could pursue science, whether I could
pursue research, and in particular, medical research, um, in order to,
to make a difference in the world. And, and that
really was my driver at that point and has been since,
I think, making the most of the opportunities and the
education I've been given to actually do something positive and
(03:27):
make a difference in the world. And that's what led
me into medical research.
Dr Viviane Richter (03:31):
Wow, that's an incredibly powerful story. What area of medical
research did you decide to tackle from there?
Professor Benjamin Kile (03:39):
My initial foray into medical research was at the Murdoch
Children's Research Institute in Melbourne, studying birth defects, and it
was a formative moment in my life, realising that working
in a lab with lots of other people, doing experiments,
making discoveries was so much fun. I hadn't expected that.
(04:00):
I expected it to be hard work. I expected it
to be a lot of reading and thinking, and, but
realising it was actually so much fun. And just the little,
little pieces of discovery along the way were, were thrilling.
It was a real revelation, and that spurred me on
to do my PhD. And I was lucky enough to
do that in the cancer division at the Walter and
(04:21):
Eliza Hall Institute, also in Melbourne. And it was an
incredible three and a half years, again, of, of learning, training, understanding how
science works, how experiments are designed, how to analyse data, um,
how to work with colleagues, how to learn new things.
And whilst my PhD wasn't a particularly, uh, revolutionary piece
(04:42):
of work, I don't think I discovered anything of great significance. Um,
it was really uh, an incredible life-changing event in so
many ways that really set me on the path. They're
not just wanting to do more research and wanting to
understand more about blood cells and, and leukemia and, and
inflammatory disease, but the process of science itself, beginning to
(05:03):
realise that, hang on, this is a, this is a
whole way of being and thinking and doing and, and
living that was enormously exciting. And the realisation that this
was an international activity and that you could pursue this
anywhere in the world, was also a bit of a revelation.
And so, I was fortunate enough to be able to
take up a postdoctoral position at Baylor College of Medicine
(05:23):
in Houston, Texas, working with Dr Monica Justice, who is, uh,
an incredible researcher and a real force of nature. And
at that point in 2001, the human genome has almost
been completed. And so the possibility of doing large scale
gene discovery studies, uh, of the kind that Monica had
been advocating for, for decades was really coming into focus.
(05:48):
And so it was a real opportunity to, to go
to the US to be part of Monica's lab and,
and start to, to hunt for genes that regulate blood
cell development, blood cell formation and function, and, and understand
how that goes awry in, in the development of leukemia
and in inflammatory disease. So, that was an extraordinary experience. And,
and seeing the way US science works, um, the scope,
the scale, the ambition, the interaction across the, the country.
(06:11):
The international nature of it, the US sucks so many
people from across the world into their, into their research ecosystem.
And it was just that next level experience. And, and again,
I learned a lot, and it inspired me to, to
take the next step in coming back to Australia and,
and moving towards establishing my own research program.
Dr Viviane Richter (06:30):
Ben, what was Houston like?
Professor Benjamin Kile (06:32):
Houston was wild. I'd never, I'd been to America once
in my life. My wife and I got married 10
days before we moved to the US. Um, she'd never
been to the United States. And not only did we
move to the United States, we moved to Texas, and
I hadn't appreciated that Texas had been its own country
in the 1800s for about 10 years there and still
(06:53):
thinks of itself as its own country in so many ways.
And it's, it's an amazing place. It's a, it's an
amazing amalgam of, of cultures and peoples, and, um, but
also that sort of frontier mentality of ambition and scale
and juxtaposition of, of different political groups and, and attitudes.
(07:14):
It was nothing like what I expected.
Dr Viviane Richter (07:18):
So, then you decided to come back to Australia?
Professor Benjamin Kile (07:22):
We made the decision to move back in 2004, um,
and I was lucky enough to go back to the
Walter and Eliza Hall Institute and move towards ultimately establishing
my own independent research program. And that's when you, you
move from being, uh, somebody else's researcher, working primarily on
their ideas to starting to pursue the questions that you
(07:43):
find most interesting, which is an enormous amount of fun.
And I was taking some of the ideas I'd learned
in Texas and applying them to, to different types of
genetic screens back in Melbourne. And as science tends to unfold,
I went looking for one thing and I found something else.
We were looking for things that regulate the formation of
(08:03):
blood cells, the production of blood cells, and ultimately wound
up finding something responsible for killing blood cells. Um, and
in particular type of blood cell, the platelet, which is the,
the tiny, tiny blood cell that's responsible for blood clotting
in response, uh, to a wound. That sounds rather esoteric,
but the, the role of platelets and the role of
(08:25):
the factors that regulate their lifespan is something that's been
studied since the early 1900s, in fact, because they're incredibly short-lived.
Unlike other blood cells, they only live for a matter
of days. And so their production and, and their lifespan's
been a, a real mystery. And that came into focus,
particularly in the 1960s as cancer chemotherapy came into practice.
Cancer chemotherapy has and, by and large, continues to do
(08:48):
a lot of damage to the blood cell system, in particular,
the production of platelets. Why is that bad? Because if
you don't have enough platelets, you tend to bleed, and
that can ultimately be catastrophic and fatal. Uh, in the
early days of cancer chemotherapy, many, many patients died of
a bleed. And that then gave rise to the birth
(09:11):
of platelet transfusion medicine. And again, we encounter the issue
of platelet life spans because you cannot store platelets for
very long at the blood bank. So there's a constant
logistical supply issue. So that's, that's a fascinating piece of history,
and people have speculated as to what regulates this short lifespan,
and we were lucky enough to, to find it. Turns
out to be a, a tiny molecular switch regulated by
(09:32):
a protein called Bcl-xL. So we're incredibly excited. We thought
this was fascinating, and we, we unpicked all the biology.
But the beautiful thing about working in a medical research
institute is there's often people around you who are doing
related things, similar things. And my colleague, David Wang, was
working to develop a new class of cancer drugs called BH3-memetics.
(09:55):
And why is that interesting? Because BH3-memetics are designed to
target a protein called Bcl-2, a friend of Bcl-xL. And
Bcl-2 has been studied for decades in the context of cancer,
particular forms of leukemia, where it's overexpressed and seen to
be playing a critical role. So, the holy grail for
David and colleagues and, and particularly the pharmaceutical industry was
(10:16):
to try and drug this protein to switch off Bcl-2
and induce the death of cancer cells. So, in talking
to David, we realised, well, it's possible that this drug
that you're working with is, is actually gonna hit Bcl-xL and,
and kill platelets. That turned out to be true. Again,
another fascinating pharmacological piece of, of the puzzle, but it
(10:37):
was particularly relevant because these drugs were about to enter
clinical trials, and it was clear to us that these
drugs were likely to kill platelets in, in cancer patients,
which is obviously a very bad thing. So those trials
were able to start with clinicians forewarned that this was
likely to happen. Sure enough, it did, and ultimately, that
became the dose-limiting toxicity, as it's known, uh, in clinical
(10:58):
trials for that drug, and that drug's development stalled. So
that was a disappointing result for all concerned. But what
our work immediately suggested was that if the drug could
be redesigned to solely target Bcl-2, not Bcl-xL, things could
move forward. And, ultimately, that's what unfolded. David and, uh,
the pharmaceutical companies Advi and Genentech redesigned this molecule to
(11:21):
create something called Venetoclax. That drug entered the trials. It
was already given at 10 times the dose of the original, um,
because it didn't kill platelets, and it roared through clinical trials.
It was a screaming success and was approved by the
FDA in 2016 for the treatment of chronic lymphocytic leukemia.
That drug has gone on to be given to thousands
(11:42):
of cancer patients. It's now being trialed in combination with
lots of other drugs. It's being trialed in solid tumors,
and it's spawned an entire field of, of new cancer
drugs that target relatives of Bcl-2 in, in different contexts
and in different combinations. So, an extraordinary piece of progress
in medical research, and I was extraordinarily lucky to play
a very small part in that process. But it, it
(12:04):
taught me a lot. It taught me that basic science,
insights into basic biology can be incredibly important to drug development.
It also showed me how medical research institutes, where you
have critical mass, you've got people with overlapping interests and
skill sets can drive things forward in unexpected ways. And
it also taught me how industry partnerships, working with drug
(12:25):
companies in particular, can be enormously powerful to translate the
research that we do at medical research institutes into actual
benefits to patients. And also that link between investigative new
drugs and basic scientists and clinicians working together to see,
not just what happens when basic science moves to the clinic,
(12:45):
but when the, the clinical results start feeding back into
the basic science. So, it really taught me a lot
about the role of medical research institutes, the role of
basic science and the, and the role of that ecosystem
effect that the places like the Walter and Eliza Hall
Institute and the Garvan represent.
Dr Viviane Richter (13:01):
Ben, what does it feel like to have contributed to
something that has made such a difference for patients?
Professor Benjamin Kile (13:07):
I can literally feel the hair standing up on the
back of my neck as I think about the day
we got the initial result that suggested we knew what
was regulating platelet lifespan. I can picture myself looking over
the shoulder of Marina Carpinelli, the postdoc who'd done the
experiment with her own hands when the two curves on
the graph started to separate and realising what we had.
(13:30):
That was the thrill of discovery, and it's hard to
describe the thrill, really. But that was, that was a discovery,
that was a piece of biology. What unfolded over the
ensuing years was entirely unpredictable to me, and even more
thrilling to see that piece of knowledge then translate into
something meaningful in patient lives, a small piece of that
greater puzzle. So, it is something that I come back
(13:53):
to regularly, when you, when you face the challenges that
that work throws at you and, and staying motivated and
trying to, to motivate others. I do often think of that,
that work and the impact that it had. It's a
great source of strength.
Dr Viviane Richter (14:05):
And it was an exciting time for genomics and medical
research in general. I heard that your lab was one
of the first in Australia to use CRISPR gene editing.
Is that right?
Professor Benjamin Kile (14:17):
My lab does believe that, in fact, that we were
one of the first to publish in Australia using CRISPR technology. Again,
a story that reflects the power of medical research institutes.
In 2013, we were trying to unpick the mechanisms by which, again,
cancer drugs induce cell death and, and how that impacts
the way cells die, and the way cells die influencing
(14:40):
then subsequent immune responses. And we were searching for experimental
systems that would now enable us to, to test a
particular hypothesis. And a, a colleague next door, Marco Herald, um,
who's a real early adopter of technology, had, had taken
on the CRISPR system and was trying to figure out
how to use it, how to develop it and adapt it,
(15:01):
and had done a lot of work. And he generously
supplied us with the bits and pieces and instructions on
how to, to make it work for our system. Within weeks,
we'd been able to manipulate cells in a way we'd
never been able to do it before. It was, it
was literally like magic, and we had a system that
could test our hypothesis, and that work was published in 2014,
(15:21):
which is only three years after the initial discovery by
the Doudna Lab and others. And so, we certainly didn't
discover CRISPR and we certainly haven't done extraordinary evolution in
CRISPR technology, but I do think we were one of
the first in Australia to actually generate experimental data with it.
Dr Viviane Richter (15:36):
So since then, you've had an incredible career moving from
research into research leadership, WEHI, Monash, the University of Adelaide.
What led you to Garvan?
Professor Benjamin Kile (15:51):
Well, Garvan's a, a world-class medical research institute, and medical
research institutes, or MRIs as we call them, occupy a,
a really important and special place in the medical research
landscape in Australia. Um, I grew up at the Walter
and Eliza Hall Institute, WEHI, and Garvan was always considered
our sister institute in many ways. Founded 60 years ago,
(16:13):
it's been incredibly strong in areas like diabetes, bone research, cancer, immunology, neuroscience,
genomics and, and genetics. And so, it's a place I knew. I
knew many friends and colleagues at Garvan and followed it
with great interest over the years. So, when the opportunity
came to, to move to Garvan, to take on the
leadership and to take Garvan forward, I still pinch myself
(16:36):
that I've been given this, this opportunity. It's a real,
real honour and a real privilege to be handed the
reins of Garvan.
Dr Viviane Richter (16:42):
What is a medical research institute, say, compared to a
university or a pharmaceutical company who are also doing medical research?
Professor Benjamin Kile (16:51):
Well, Garvan is a medical research institute and, importantly, an
independent medical research institute. We're a non-for-profit organisation that has a
single focus, and that is medical research, making discoveries, translating
them into the clinic. Our researchers do what's known as
investigator-led research, which means they get to decide which questions
(17:12):
they think are the most important, which approaches they think
are gonna be the most valuable, which technologies they think
we need to apply. So it gives them enormous freedom
to operate. They're driven by passion. The single focus, I think,
is the most important thing. We have no other business
but making discovery and translating that into impact for patients.
Dr Viviane Richter (17:32):
So, Ben, what is the perfect recipe for a productive,
thriving medical research institute?
Professor Benjamin Kile (17:40):
It's a great question, Viv, and, and one that keeps
me awake at night. And I think it starts obviously
with people, world-class people, scientists, clinicians and professional staff, because
it's an ecosystem that needs to be supported by all
the elements of operations that you'd imagine, and we're very
blessed at Garvan with the, the caliber of people that
we have. Thinking about clinicians and clinician researchers, it, it
(18:03):
is important that a place like Garvan isn't just basic science.
We are built on a foundation of basic science, 60
years of extraordinary basic science, but we are about ultimately
translating that science into impacting patient lives. So, operating in
an ecosystem where we have clinicians and clinician researchers as
part of the organisation is critically important, I think, for
(18:25):
success in medical research these days. Having clinicians who are
involved in not just clinical care, but clinical trials, um,
having clinician researchers who are involved in patient care, but
understand the basic science that's around them and can inform
that science, and vice versa, is absolutely critically important, as
we've moved from an era where studying human biology was hard,
(18:48):
and so we did a lot of work in fish
and flies and mice, and that's been absolutely foundational and
fundamental and continues. But, the ability to study human biology
now is, is very much driven by patients, patient care
and clinical trials, and that intersection with basic science. And again,
Garvan has those elements and, um, is very fortunate. I
(19:10):
think you also need to focus the days of institutions
being able to work on dozens of different diseases effectively,
are gone. You really need multiple groups working in key
disease areas with a focus and sharing insights, speaking a
common language, sharing reagents and ideas. And for us, those
three areas are cancer, genomics and immunology, and that focus
(19:32):
element is, is really, really important. And then the other
piece of the puzzle is technology. Um, you cannot afford
your researchers to be dealing with suboptimal, um, experimental systems,
to be using technology that won't yield the sort of
analytical insights that's expected if we're gonna make transformative discoveries.
So investing in technology, knowing which technologies to invest in,
(19:53):
and working, uh, as an institute to ensure that we're
providing that to our researchers is, is absolutely key if
you're gonna be internationally competitive.
Dr Viviane Richter (20:02):
Ben, you've just released your strategy for the Institute. Tell
us the specifics. What will change at, Garvan?
Professor Benjamin Kile (20:10):
Well, a new leader obviously brings a fresh perspective, and
I think, periodically, the Institute needs to renew and refresh
its vision, and, and that's what we've done. I've talked
about cancer, genomics and immunology as, as our strengths, and
they are our strengths, and that's evolved naturally and, also,
deliberately over the last decade. They are our strengths. They
(20:32):
represent our ambitions and they also, um, in some ways
parallel some of the major developments in medical research, um,
which puts us in a very fortunate position. To begin with,
genomics has, has, since the human genome was sequenced in
the early 2000s, become absolutely foundational to biology and medical research.
Not just understanding the genome, but the different approaches that
(20:55):
enable us to unpack the way biology works, the way
disease works. Genomics is, is foundational, and Garvan is very
fortunate to be in the position it's in, in that field.
We're very, very strong in immunology, particularly when it comes to,
to things like autoimmune disease. And we're very fortunate in
that sense, because over the last 20 years, we've begun
to appreciate that immunology is central to every human disease.
(21:20):
Every human disease is touched on, impacted by, intersects with,
can be treated by the immune system. It's been an
extraordinary revelation to those of us who didn't train as
immunologists to see how central the immune system has become
to our, our way of viewing human disease. And cancer research, well,
cancer research is the major driver of medical research. Not
(21:44):
only is it a motivator for so many people, um,
it's a huge burden of disease, and it drives medical
research forward. So much of what happens in cancer turns
out to have relevance in other disease settings. So many
cancer therapies turn out to have application in other diseases,
and cancer demands technological advances. It's such a big field.
(22:06):
There are so many people working in it, that there's
a constant drive from cancer research for new ways of
looking at things, new analytical tools, new approaches. So, for
an institution like Garvan to, to be strong in cancer,
to be expanding its cancer research is, is really important.
So if you put those three things together and think
of it as a triangle, it's a great triangle of
(22:27):
strength and focus. What we've done over the last decade
is integrate genomics and immunology really, really effectively. And we've
integrated genomics in cancer really, really effectively. But what we
haven't done is integrate our strengths in cancer and immunology.
And most of you will know, most of our listeners
will know that over the last 15 years, the biggest
(22:49):
development in cancer research and cancer treatment has been the
rise of the so-called 'cancer immunotherapies' – a whole raft of
new tools, new experimental and, now, approved therapies that are
being deployed to harness the immune system to cure cancer. So,
for Garvan, you know, there's an extraordinary opportunity to, to
grow into that space and to recruit. Uh, one of
(23:10):
the things any institute director is excited about is recruiting
new talent to the institute, particularly young folks from around
Australia and internationally, and we're beginning to, to do that now.
It is one of the great joys, I think, to
see bright young people come into science, come into the institute,
bring their ideas, to realise the excitement around them and
the possibilities and to to start to do things differently
(23:33):
and challenge more established researchers, build collaborations, and it's probably
the thing that I'm absolutely most excited about, uh, for
the future of Garvan under the new strategy.
Dr Viviane Richter (23:43):
Translation is a key aspect of your strategy. Tell us
about that.
Professor Benjamin Kile (23:49):
Well, translation is, is simply turning knowledge into patient impacts
– something Garvan has always done since the 60s when it was
founded by the Sisters of Charity. But one of the
things we're increasingly focused on is building the technological capabilities
that will enable us to start creating what are called
tool compounds, experimental therapies, the kind of discoveries and reagents
(24:13):
that will move towards ultimately becoming new medicines. It's not
something Garvan has probably done as much of as you
might expect, and I think it's a huge opportunity for
us to be getting our hands dirty, creating new medicines,
experimental medicines, and starting to partner more effectively with, with biotech,
with pharma, um, with venture capital to move those things
towards ultimately clinical trials. I'd like to see Garvan, 10
(24:37):
years from now, be celebrating the fact that there are
new medicines that have been approved that had their origins
in Garvan science.
Dr Viviane Richter (24:44):
What research at Garvan are you really excited about at
the moment then?
Professor Benjamin Kile (24:48):
So much, so much, so many things, and, and it's
always dangerous to, for the director to start talking about
what they're excited about. We are extraordinarily strong in pancreatic
cancer research, and with people like Marina Pajic, um, and
Anthony Joshua, Paul Timpson pushing towards clinical trials, taking drugs
that have either been used in other settings or are
(25:09):
still finding their way through the clinic and starting to
identify novel opportunities to treat pancreatic cancer. There's a lot
happening in the context of autoimmunity, um, in the context
of trying to understand the sex spikes differences, uh, in
predisposition to autoimmune disease. But also in things to do
with B cells and the role B cells play in
cancer and, potentially, cancer immunotherapy. We know a lot about
(25:32):
T cells. You may have heard about CAR T cells
being used to treat cancer, but the role of B cells,
the other important lymphocyte counterpart to them is unclear, and
I think some research happening at Garvan promises to shed
new light and new therapeutic possibilities on that. Also in
the cancer space, there's some intriguing new research being done
by one of our new recruits, Ankur Sharma, who's looking
(25:53):
at the, the way liver cancer seems to reprogram the
tumour microenvironment to resemble what turns out to be quite
similar to the fetal liver, for reasons we simply don't understand,
but suggests all kinds of intriguing possibilities around new therapies.
There's so much happening at Garvan, and so much of
it's driven by our younger researchers, um, which is, I think,
(26:14):
incredibly exciting and, and really does point to a bright
future for the Institute.
Dr Viviane Richter (26:18):
What about genomics?
Professor Benjamin Kile (26:19):
Genomics is one of our great strengths, and I think
the exciting thing about the genomics happening at Garvan at
the moment is we span everything from monogenic disorders, so
trying to understand rare diseases in single patients and in
single families, through to population genomics under Daniel MacArthur, trying
to understand and build out an atlas of human variation,
(26:39):
which will enable so much progress in enabling the application
of precision medicine ultimately in the healthcare system. But we're
also now, under Joseph Powell, drilling down into single cells
and how single genes are regulated in single cell types,
which is, uh, a hitherto, um, impossible task that Joseph's
now pulling apart and elucidating. That's important because it starts
(27:03):
to get at the, the nuance of complex human diseases
like cardiovascular disease, diabetes and others. So, the level of
sophistication and detail being applied there, I think is, it
is absolutely cutting edge and it's, it offers so many
possibilities to understanding how these diseases, which have been studied
for decades and studied at a genetic level for decades,
(27:23):
but it's still out of reach, I think that's an
incredibly exciting area.
Dr Viviane Richter (27:37):
With so much exciting research happening at Garvan, I think what really has struck me at my time at Garvan is the sense of community around the Institute. Have you felt the same way?
Professor Benjamin Kile (27:38):
I, I totally agree, Viv. It's been one of the
most exciting aspects for me coming to Garvan. Obviously, I
was well aware of Garvan, what it represents, the research,
the researchers, um, but I hadn't quite appreciated the place
it holds within the landscape in, in New South Wales and,
and the relationship it has with the community. We depend
on community support to do what we do. I've often said,
(28:00):
we turn public support into public knowledge, and ideally that
knowledge can then be translated into impacting patient lives. But
the degree to which Garvan is integrated into the community
and the level of support and the support that, in
some cases, some families goes back two or even three
generations has been a revelation to me. I've not seen
(28:23):
that before in, in Australia, so, realising what Garvan represents
to people has been a real thrill. Also creates a
real sense of obligation. You know, we're here, as I
keep saying, to make an impact, so the support that
we get really engenders in me and, I think, the
folks at Garvan, a sense of obligation to really deliver, and
we're gonna be increasingly focused on that in the decade
(28:44):
to come.
Dr Viviane Richter (28:45):
So what do you see as the key challenges for Garvan?
Professor Benjamin Kile (28:49):
I think the major challenge, Viv, is supporting the careers of
individual researchers. We've seen over the 27 years I've been
in medical research, the dissipation of, of many of the
career structures that used to be supported by funding agencies,
particularly in this country. You've seen the rise of, of
team science, of consortium science, and an increasing emphasis on
(29:10):
multi-disciplinary teams, etc. which is all wonderful. But it does
make it hard for individual researchers to sustain their careers.
And I think younger researchers looking upwards now really do
wonder how on earth they're gonna be able to fashion
a lifetime in research. And Garvan's challenge is to support
younger researchers, in particular, to enable them, to mentor them,
(29:33):
develop them. The system in Australia is radically underfunded. So
the financial sustainability challenge is ever-present, not just for supporting
individual researchers, but for developing the technology we need, um,
and supporting all the professional systems that, that make Garvan happen. So, ultimately,
it is a financial sustainability challenge.
Dr Viviane Richter (29:55):
Ben, if we dial back to 20 years ago, we
would have just witnessed the completion of the first human genome.
Say if we dial forward 20 years, what impact do
you think Garvan will have had?
Professor Benjamin Kile (30:09):
I see myriad opportunities, and I've talked about a few
aspects of the research that really excite me at the moment.
I think in autoimmune disease, our researchers talk about treating
patients with the right drug at the right time. Precision immunology,
if you will. And I, I think that is a,
a very real prospect. Great progress has been made in
cancer research in identifying the specific causes of a particular
(30:32):
patient's tumour and, and matching them with therapy. I think
we'll see that in autoimmune disease. I think within 20 years,
it is entirely conceivable that most, if not all, autoimmune
diseases will be treatable, if not ultimately cured. I think
Garvan has a big role to play there. If you
look at pancreatic cancer, I would hope that 20 years
from now, the enormous effort that Garvan is putting in
(30:55):
and the enormous talent that we have in that space
will have yielded massive differences in the ability to treat
pancreatic cancer. It is a very nasty disease. And I
think the, the level of technological sophistication we're bringing to
that space will ultimately yield major progress. On the genomic
side of things, there is no doubt that 20 years
from now, we will have, I think, nailed down the
(31:19):
genetic causes of every rare disease, and I think we'll
be making real progress in treating some of those diseases.
And on the complex genomic side of it, the sort
of single-cell approaches that people like Joseph Powell are developing,
I do think there will be different ways of treating
complex diseases that are, that we can't encapsulate at this point.
(31:39):
We just don't know what they are, but there's no
doubt that the nuance and sophistication of understanding those complex
diseases will be much, much further advanced, as will the
therapeutic advances. And I think Garvan should be looking back at,
as I've said, medicines that had their origins in Garvan science.
I was asked this question at a, at a staff
meeting recently, and it dawned on me after the event
(32:01):
that I think one of the things I'm most excited about,
and I wish I could travel forwards in time, are
the discoveries that I can't imagine that the folks at
Garvan can't imagine. The beautiful thing about science is it's unpredictability,
the serendipitous, the synergistic discoveries, and scientific progress is littered
with those moments. And I'm looking forward to two decades
(32:23):
of those at Garvan, just seeing what those discoveries are.
Those things that 50 years from now, people will say, oh,
that was discovered at Garvan. That concept, that idea, that possibility,
that happened at Garvan. To finish where I started up
makes the hair stand up on the back of my neck.
Dr Viviane Richter (32:39):
Ben, you lead a medical research institute of 700 staff.
What drives you day to day and how do you
inspire the people that work at Garvan?
Professor Benjamin Kile (32:49):
I hope to inspire the people who work at Garvan.
What drives me is, is the same thing that drove
me into doing an honors project in 1997, which is
the desire to make a difference. Obviously, I find science
invigorating and exciting, but it's the impact that science makes
that drives me, the impact of medical research. Watching over
(33:09):
27 years in, in my career, the, the progress that's
been made in, in different disease areas is, is just
absolutely phenomenal. And so I remain as excited about medical
research as I have ever been. And so it's not
hard to get motivated. I stand up and I talk
at Garvan about what we're doing and people sometimes comment,
"It all sounds authentic, Ben." And that's because I'm simply
(33:32):
saying what I think and what I feel. So getting
motivated is not hard, and I hope that, that, you know, enthusiasm,
that inspiration, um, does inspire Garvan people. What I find though,
is that across the Institute, whether it's the folks who
work on the front desk, whether it's the people in
the mouse house, the people on the finance team, the
people in the research labs, people in fundraising, wherever you look,
(33:54):
you find people who are innately motivated by the possibilities
of medical research, and by the possibilities of Garvan. I
don't have to inspire everyone who works at Garvan. I
don't have to inspire our supporters. I try, um, and
I try and bring them together and support them, but
that innate passion and enthusiasm for medical research and, and
(34:14):
progress in, in making a difference in patients' lives is
there in, in so many people at Garvan.
Dr Viviane Richter (34:20):
Professor Benjamin Kile, thank you so much for joining us
on Medical Minds.
Professor Benjamin Kile (34:25):
It's been an absolute pleasure. Thank you for having me.
Dr Viviane Richter (34:27):
If you'd like to know more about Garvan's research or
donate to the work we do, head to garvan.org.au. And
if you've enjoyed this podcast, please leave a review and
share with other podcast lovers. I'm Dr Viviane Richter. Thanks for listening. This podcast was recorded on the traditional Country of the Gadigal people of the Eora Nation. We recognise their continuing connection to land, waters and community. We pay our respects to Aboriginal and Torres Strait Islander cultures and Elders past, present and emerging.
On this podcast, we've met more than 25 researchers from Garvan,
each working on the next game changers for cancer, immune
disease and inherited genetic conditions, amongst others. But we've never
sat down for a chat with our leader. Professor Benjamin
Kile is an accomplished molecular biologist, internationally recognised for his
(00:23):
research in blood cell development that informed a major breakthrough
for cancer treatment. Benjamin has a vision for Garvan to
accelerate and empower fundamental biomedical research that will lead to
better prevention, treatment and, ultimately, cures for disease. So, what
does that mean and how will Garvan get there? Welcome
(00:45):
to Medical Minds, the podcast that takes you inside the
labs at the Garvan Institute of Medical Research. I'm your host,
Dr Viviane Richter, and it is a huge pleasure to
have in the studio today Garvan Executive Director, Professor Benjamin Kile. Welcome, Ben.
Professor Benjamin Kile (01:02):
Thank you, Viviane. Wonderful to be here.
Dr Viviane Richter (01:04):
Ben, before we talk about how you came to be
at the helm of one of the biggest medical research
institutes in Australia, I'd love to know how it all
started for you. Did you always know you were gonna
be a scientist?
Professor Benjamin Kile (01:16):
Well, in hindsight, perhaps it was, it was obvious, but
growing up, I don't think it was. I was always
interested in the world. I was always interested in history.
And as a young person, I had a series of passions, obsessions,
I guess you could call them. Uh, when I was,
in primary school, I was fascinated by ancient Egypt, and,
when I realised there were such people as archaeologists, I
(01:38):
was determined to be one. Later in life, I, I
became really, really interested in, in astronomy. I guess, in part,
driven by that wonderful Carl Sagan series, Cosmos, and for many,
many years, wanted to be an astronomer-slash-astronaut. And then, at school,
high school in grade 8, doing biology, I was introduced
(02:00):
to the concept of genes, and that was a really
signal moment in my life, realising that there were things
called genes embedded in your DNA that, uh, regulated the
program of life. And I think from that point on
it was always I was always interested in biology, but
didn't really know where that was leading. I didn't really
know what scientists did. I didn't really know what research was.
(02:22):
So when I went to university in the early 90s,
I ended up doing a combination science and law degree.
With the words of my parents ringing in my ears,
I was keeping my options open. I didn't really know
where my career was headed. And it was towards the
end of my, my two degrees that I experienced, I guess,
the first loss of someone close to me who, who
(02:43):
wasn't a grandparent, whose death really seemed to interrupt the
natural order of things. And that was my uncle, um,
who was one of the sort of formative people in
my life. He was an extraordinary character, larger than life, and, um,
full of energy and art and politics, and just a,
a real inspiration to me. And in 1994, he died
of AIDS, and that was shocking. And it wasn't a
(03:06):
light bulb moment in the sense that it, it signaled
to me what I needed to do with my life,
but I guess over the years that followed, I started
to wonder whether I could pursue science, whether I could
pursue research, and in particular, medical research, um, in order to,
to make a difference in the world. And, and that
really was my driver at that point and has been since,
I think, making the most of the opportunities and the
education I've been given to actually do something positive and
(03:27):
make a difference in the world. And that's what led
me into medical research.
Dr Viviane Richter (03:31):
Wow, that's an incredibly powerful story. What area of medical
research did you decide to tackle from there?
Professor Benjamin Kile (03:39):
My initial foray into medical research was at the Murdoch
Children's Research Institute in Melbourne, studying birth defects, and it
was a formative moment in my life, realising that working
in a lab with lots of other people, doing experiments,
making discoveries was so much fun. I hadn't expected that.
(04:00):
I expected it to be hard work. I expected it
to be a lot of reading and thinking, and, but
realising it was actually so much fun. And just the little,
little pieces of discovery along the way were, were thrilling.
It was a real revelation, and that spurred me on
to do my PhD. And I was lucky enough to
do that in the cancer division at the Walter and
(04:21):
Eliza Hall Institute, also in Melbourne. And it was an
incredible three and a half years, again, of, of learning, training, understanding how
science works, how experiments are designed, how to analyse data, um,
how to work with colleagues, how to learn new things.
And whilst my PhD wasn't a particularly, uh, revolutionary piece
(04:42):
of work, I don't think I discovered anything of great significance. Um,
it was really uh, an incredible life-changing event in so
many ways that really set me on the path. They're
not just wanting to do more research and wanting to
understand more about blood cells and, and leukemia and, and
inflammatory disease, but the process of science itself, beginning to
(05:03):
realise that, hang on, this is a, this is a
whole way of being and thinking and doing and, and
living that was enormously exciting. And the realisation that this
was an international activity and that you could pursue this
anywhere in the world, was also a bit of a revelation.
And so, I was fortunate enough to be able to
take up a postdoctoral position at Baylor College of Medicine
(05:23):
in Houston, Texas, working with Dr Monica Justice, who is, uh,
an incredible researcher and a real force of nature. And
at that point in 2001, the human genome has almost
been completed. And so the possibility of doing large scale
gene discovery studies, uh, of the kind that Monica had
been advocating for, for decades was really coming into focus.
(05:48):
And so it was a real opportunity to, to go
to the US to be part of Monica's lab and,
and start to, to hunt for genes that regulate blood
cell development, blood cell formation and function, and, and understand
how that goes awry in, in the development of leukemia
and in inflammatory disease. So, that was an extraordinary experience. And,
and seeing the way US science works, um, the scope,
the scale, the ambition, the interaction across the, the country.
(06:11):
The international nature of it, the US sucks so many
people from across the world into their, into their research ecosystem.
And it was just that next level experience. And, and again,
I learned a lot, and it inspired me to, to
take the next step in coming back to Australia and,
and moving towards establishing my own research program.
Dr Viviane Richter (06:30):
Ben, what was Houston like?
Professor Benjamin Kile (06:32):
Houston was wild. I'd never, I'd been to America once
in my life. My wife and I got married 10
days before we moved to the US. Um, she'd never
been to the United States. And not only did we
move to the United States, we moved to Texas, and
I hadn't appreciated that Texas had been its own country
in the 1800s for about 10 years there and still
(06:53):
thinks of itself as its own country in so many ways.
And it's, it's an amazing place. It's a, it's an
amazing amalgam of, of cultures and peoples, and, um, but
also that sort of frontier mentality of ambition and scale
and juxtaposition of, of different political groups and, and attitudes.
(07:14):
It was nothing like what I expected.
Dr Viviane Richter (07:18):
So, then you decided to come back to Australia?
Professor Benjamin Kile (07:22):
We made the decision to move back in 2004, um,
and I was lucky enough to go back to the
Walter and Eliza Hall Institute and move towards ultimately establishing
my own independent research program. And that's when you, you
move from being, uh, somebody else's researcher, working primarily on
their ideas to starting to pursue the questions that you
(07:43):
find most interesting, which is an enormous amount of fun.
And I was taking some of the ideas I'd learned
in Texas and applying them to, to different types of
genetic screens back in Melbourne. And as science tends to unfold,
I went looking for one thing and I found something else.
We were looking for things that regulate the formation of
(08:03):
blood cells, the production of blood cells, and ultimately wound
up finding something responsible for killing blood cells. Um, and
in particular type of blood cell, the platelet, which is the,
the tiny, tiny blood cell that's responsible for blood clotting
in response, uh, to a wound. That sounds rather esoteric,
but the, the role of platelets and the role of
(08:25):
the factors that regulate their lifespan is something that's been
studied since the early 1900s, in fact, because they're incredibly short-lived.
Unlike other blood cells, they only live for a matter
of days. And so their production and, and their lifespan's
been a, a real mystery. And that came into focus,
particularly in the 1960s as cancer chemotherapy came into practice.
Cancer chemotherapy has and, by and large, continues to do
(08:48):
a lot of damage to the blood cell system, in particular,
the production of platelets. Why is that bad? Because if
you don't have enough platelets, you tend to bleed, and
that can ultimately be catastrophic and fatal. Uh, in the
early days of cancer chemotherapy, many, many patients died of
a bleed. And that then gave rise to the birth
(09:11):
of platelet transfusion medicine. And again, we encounter the issue
of platelet life spans because you cannot store platelets for
very long at the blood bank. So there's a constant
logistical supply issue. So that's, that's a fascinating piece of history,
and people have speculated as to what regulates this short lifespan,
and we were lucky enough to, to find it. Turns
out to be a, a tiny molecular switch regulated by
(09:32):
a protein called Bcl-xL. So we're incredibly excited. We thought
this was fascinating, and we, we unpicked all the biology.
But the beautiful thing about working in a medical research
institute is there's often people around you who are doing
related things, similar things. And my colleague, David Wang, was
working to develop a new class of cancer drugs called BH3-memetics.
(09:55):
And why is that interesting? Because BH3-memetics are designed to
target a protein called Bcl-2, a friend of Bcl-xL. And
Bcl-2 has been studied for decades in the context of cancer,
particular forms of leukemia, where it's overexpressed and seen to
be playing a critical role. So, the holy grail for
David and colleagues and, and particularly the pharmaceutical industry was
(10:16):
to try and drug this protein to switch off Bcl-2
and induce the death of cancer cells. So, in talking
to David, we realised, well, it's possible that this drug
that you're working with is, is actually gonna hit Bcl-xL and,
and kill platelets. That turned out to be true. Again,
another fascinating pharmacological piece of, of the puzzle, but it
(10:37):
was particularly relevant because these drugs were about to enter
clinical trials, and it was clear to us that these
drugs were likely to kill platelets in, in cancer patients,
which is obviously a very bad thing. So those trials
were able to start with clinicians forewarned that this was
likely to happen. Sure enough, it did, and ultimately, that
became the dose-limiting toxicity, as it's known, uh, in clinical
(10:58):
trials for that drug, and that drug's development stalled. So
that was a disappointing result for all concerned. But what
our work immediately suggested was that if the drug could
be redesigned to solely target Bcl-2, not Bcl-xL, things could
move forward. And, ultimately, that's what unfolded. David and, uh,
the pharmaceutical companies Advi and Genentech redesigned this molecule to
(11:21):
create something called Venetoclax. That drug entered the trials. It
was already given at 10 times the dose of the original, um,
because it didn't kill platelets, and it roared through clinical trials.
It was a screaming success and was approved by the
FDA in 2016 for the treatment of chronic lymphocytic leukemia.
That drug has gone on to be given to thousands
(11:42):
of cancer patients. It's now being trialed in combination with
lots of other drugs. It's being trialed in solid tumors,
and it's spawned an entire field of, of new cancer
drugs that target relatives of Bcl-2 in, in different contexts
and in different combinations. So, an extraordinary piece of progress
in medical research, and I was extraordinarily lucky to play
a very small part in that process. But it, it
(12:04):
taught me a lot. It taught me that basic science,
insights into basic biology can be incredibly important to drug development.
It also showed me how medical research institutes, where you
have critical mass, you've got people with overlapping interests and
skill sets can drive things forward in unexpected ways. And
it also taught me how industry partnerships, working with drug
(12:25):
companies in particular, can be enormously powerful to translate the
research that we do at medical research institutes into actual
benefits to patients. And also that link between investigative new
drugs and basic scientists and clinicians working together to see,
not just what happens when basic science moves to the clinic,
(12:45):
but when the, the clinical results start feeding back into
the basic science. So, it really taught me a lot
about the role of medical research institutes, the role of
basic science and the, and the role of that ecosystem
effect that the places like the Walter and Eliza Hall
Institute and the Garvan represent.
Dr Viviane Richter (13:01):
Ben, what does it feel like to have contributed to
something that has made such a difference for patients?
Professor Benjamin Kile (13:07):
I can literally feel the hair standing up on the
back of my neck as I think about the day
we got the initial result that suggested we knew what
was regulating platelet lifespan. I can picture myself looking over
the shoulder of Marina Carpinelli, the postdoc who'd done the
experiment with her own hands when the two curves on
the graph started to separate and realising what we had.
(13:30):
That was the thrill of discovery, and it's hard to
describe the thrill, really. But that was, that was a discovery,
that was a piece of biology. What unfolded over the
ensuing years was entirely unpredictable to me, and even more
thrilling to see that piece of knowledge then translate into
something meaningful in patient lives, a small piece of that
greater puzzle. So, it is something that I come back
(13:53):
to regularly, when you, when you face the challenges that
that work throws at you and, and staying motivated and
trying to, to motivate others. I do often think of that,
that work and the impact that it had. It's a
great source of strength.
Dr Viviane Richter (14:05):
And it was an exciting time for genomics and medical
research in general. I heard that your lab was one
of the first in Australia to use CRISPR gene editing.
Is that right?
Professor Benjamin Kile (14:17):
My lab does believe that, in fact, that we were
one of the first to publish in Australia using CRISPR technology. Again,
a story that reflects the power of medical research institutes.
In 2013, we were trying to unpick the mechanisms by which, again,
cancer drugs induce cell death and, and how that impacts
the way cells die, and the way cells die influencing
(14:40):
then subsequent immune responses. And we were searching for experimental
systems that would now enable us to, to test a
particular hypothesis. And a, a colleague next door, Marco Herald, um,
who's a real early adopter of technology, had, had taken
on the CRISPR system and was trying to figure out
how to use it, how to develop it and adapt it,
(15:01):
and had done a lot of work. And he generously
supplied us with the bits and pieces and instructions on
how to, to make it work for our system. Within weeks,
we'd been able to manipulate cells in a way we'd
never been able to do it before. It was, it
was literally like magic, and we had a system that
could test our hypothesis, and that work was published in 2014,
(15:21):
which is only three years after the initial discovery by
the Doudna Lab and others. And so, we certainly didn't
discover CRISPR and we certainly haven't done extraordinary evolution in
CRISPR technology, but I do think we were one of
the first in Australia to actually generate experimental data with it.
Dr Viviane Richter (15:36):
So since then, you've had an incredible career moving from
research into research leadership, WEHI, Monash, the University of Adelaide.
What led you to Garvan?
Professor Benjamin Kile (15:51):
Well, Garvan's a, a world-class medical research institute, and medical
research institutes, or MRIs as we call them, occupy a,
a really important and special place in the medical research
landscape in Australia. Um, I grew up at the Walter
and Eliza Hall Institute, WEHI, and Garvan was always considered
our sister institute in many ways. Founded 60 years ago,
(16:13):
it's been incredibly strong in areas like diabetes, bone research, cancer, immunology, neuroscience,
genomics and, and genetics. And so, it's a place I knew. I
knew many friends and colleagues at Garvan and followed it
with great interest over the years. So, when the opportunity
came to, to move to Garvan, to take on the
leadership and to take Garvan forward, I still pinch myself
(16:36):
that I've been given this, this opportunity. It's a real,
real honour and a real privilege to be handed the
reins of Garvan.
Dr Viviane Richter (16:42):
What is a medical research institute, say, compared to a
university or a pharmaceutical company who are also doing medical research?
Professor Benjamin Kile (16:51):
Well, Garvan is a medical research institute and, importantly, an
independent medical research institute. We're a non-for-profit organisation that has a
single focus, and that is medical research, making discoveries, translating
them into the clinic. Our researchers do what's known as
investigator-led research, which means they get to decide which questions
(17:12):
they think are the most important, which approaches they think
are gonna be the most valuable, which technologies they think
we need to apply. So it gives them enormous freedom
to operate. They're driven by passion. The single focus, I think,
is the most important thing. We have no other business
but making discovery and translating that into impact for patients.
Dr Viviane Richter (17:32):
So, Ben, what is the perfect recipe for a productive,
thriving medical research institute?
Professor Benjamin Kile (17:40):
It's a great question, Viv, and, and one that keeps
me awake at night. And I think it starts obviously
with people, world-class people, scientists, clinicians and professional staff, because
it's an ecosystem that needs to be supported by all
the elements of operations that you'd imagine, and we're very
blessed at Garvan with the, the caliber of people that
we have. Thinking about clinicians and clinician researchers, it, it
(18:03):
is important that a place like Garvan isn't just basic science.
We are built on a foundation of basic science, 60
years of extraordinary basic science, but we are about ultimately
translating that science into impacting patient lives. So, operating in
an ecosystem where we have clinicians and clinician researchers as
part of the organisation is critically important, I think, for
(18:25):
success in medical research these days. Having clinicians who are
involved in not just clinical care, but clinical trials, um,
having clinician researchers who are involved in patient care, but
understand the basic science that's around them and can inform
that science, and vice versa, is absolutely critically important, as
we've moved from an era where studying human biology was hard,
(18:48):
and so we did a lot of work in fish
and flies and mice, and that's been absolutely foundational and
fundamental and continues. But, the ability to study human biology
now is, is very much driven by patients, patient care
and clinical trials, and that intersection with basic science. And again,
Garvan has those elements and, um, is very fortunate. I
(19:10):
think you also need to focus the days of institutions
being able to work on dozens of different diseases effectively,
are gone. You really need multiple groups working in key
disease areas with a focus and sharing insights, speaking a
common language, sharing reagents and ideas. And for us, those
three areas are cancer, genomics and immunology, and that focus
(19:32):
element is, is really, really important. And then the other
piece of the puzzle is technology. Um, you cannot afford
your researchers to be dealing with suboptimal, um, experimental systems,
to be using technology that won't yield the sort of
analytical insights that's expected if we're gonna make transformative discoveries.
So investing in technology, knowing which technologies to invest in,
(19:53):
and working, uh, as an institute to ensure that we're
providing that to our researchers is, is absolutely key if
you're gonna be internationally competitive.
Dr Viviane Richter (20:02):
Ben, you've just released your strategy for the Institute. Tell
us the specifics. What will change at, Garvan?
Professor Benjamin Kile (20:10):
Well, a new leader obviously brings a fresh perspective, and
I think, periodically, the Institute needs to renew and refresh
its vision, and, and that's what we've done. I've talked
about cancer, genomics and immunology as, as our strengths, and
they are our strengths, and that's evolved naturally and, also,
deliberately over the last decade. They are our strengths. They
(20:32):
represent our ambitions and they also, um, in some ways
parallel some of the major developments in medical research, um,
which puts us in a very fortunate position. To begin with,
genomics has, has, since the human genome was sequenced in
the early 2000s, become absolutely foundational to biology and medical research.
Not just understanding the genome, but the different approaches that
(20:55):
enable us to unpack the way biology works, the way
disease works. Genomics is, is foundational, and Garvan is very
fortunate to be in the position it's in, in that field.
We're very, very strong in immunology, particularly when it comes to,
to things like autoimmune disease. And we're very fortunate in
that sense, because over the last 20 years, we've begun
to appreciate that immunology is central to every human disease.
(21:20):
Every human disease is touched on, impacted by, intersects with,
can be treated by the immune system. It's been an
extraordinary revelation to those of us who didn't train as
immunologists to see how central the immune system has become
to our, our way of viewing human disease. And cancer research, well,
cancer research is the major driver of medical research. Not
(21:44):
only is it a motivator for so many people, um,
it's a huge burden of disease, and it drives medical
research forward. So much of what happens in cancer turns
out to have relevance in other disease settings. So many
cancer therapies turn out to have application in other diseases,
and cancer demands technological advances. It's such a big field.
(22:06):
There are so many people working in it, that there's
a constant drive from cancer research for new ways of
looking at things, new analytical tools, new approaches. So, for
an institution like Garvan to, to be strong in cancer,
to be expanding its cancer research is, is really important.
So if you put those three things together and think
of it as a triangle, it's a great triangle of
(22:27):
strength and focus. What we've done over the last decade
is integrate genomics and immunology really, really effectively. And we've
integrated genomics in cancer really, really effectively. But what we
haven't done is integrate our strengths in cancer and immunology.
And most of you will know, most of our listeners
will know that over the last 15 years, the biggest
(22:49):
development in cancer research and cancer treatment has been the
rise of the so-called 'cancer immunotherapies' – a whole raft of
new tools, new experimental and, now, approved therapies that are
being deployed to harness the immune system to cure cancer. So,
for Garvan, you know, there's an extraordinary opportunity to, to
grow into that space and to recruit. Uh, one of
(23:10):
the things any institute director is excited about is recruiting
new talent to the institute, particularly young folks from around
Australia and internationally, and we're beginning to, to do that now.
It is one of the great joys, I think, to
see bright young people come into science, come into the institute,
bring their ideas, to realise the excitement around them and
the possibilities and to to start to do things differently
(23:33):
and challenge more established researchers, build collaborations, and it's probably
the thing that I'm absolutely most excited about, uh, for
the future of Garvan under the new strategy.
Dr Viviane Richter (23:43):
Translation is a key aspect of your strategy. Tell us
about that.
Professor Benjamin Kile (23:49):
Well, translation is, is simply turning knowledge into patient impacts
– something Garvan has always done since the 60s when it was
founded by the Sisters of Charity. But one of the
things we're increasingly focused on is building the technological capabilities
that will enable us to start creating what are called
tool compounds, experimental therapies, the kind of discoveries and reagents
(24:13):
that will move towards ultimately becoming new medicines. It's not
something Garvan has probably done as much of as you
might expect, and I think it's a huge opportunity for
us to be getting our hands dirty, creating new medicines,
experimental medicines, and starting to partner more effectively with, with biotech,
with pharma, um, with venture capital to move those things
towards ultimately clinical trials. I'd like to see Garvan, 10
(24:37):
years from now, be celebrating the fact that there are
new medicines that have been approved that had their origins
in Garvan science.
Dr Viviane Richter (24:44):
What research at Garvan are you really excited about at
the moment then?
Professor Benjamin Kile (24:48):
So much, so much, so many things, and, and it's
always dangerous to, for the director to start talking about
what they're excited about. We are extraordinarily strong in pancreatic
cancer research, and with people like Marina Pajic, um, and
Anthony Joshua, Paul Timpson pushing towards clinical trials, taking drugs
that have either been used in other settings or are
(25:09):
still finding their way through the clinic and starting to
identify novel opportunities to treat pancreatic cancer. There's a lot
happening in the context of autoimmunity, um, in the context
of trying to understand the sex spikes differences, uh, in
predisposition to autoimmune disease. But also in things to do
with B cells and the role B cells play in
cancer and, potentially, cancer immunotherapy. We know a lot about
(25:32):
T cells. You may have heard about CAR T cells
being used to treat cancer, but the role of B cells,
the other important lymphocyte counterpart to them is unclear, and
I think some research happening at Garvan promises to shed
new light and new therapeutic possibilities on that. Also in
the cancer space, there's some intriguing new research being done
by one of our new recruits, Ankur Sharma, who's looking
(25:53):
at the, the way liver cancer seems to reprogram the
tumour microenvironment to resemble what turns out to be quite
similar to the fetal liver, for reasons we simply don't understand,
but suggests all kinds of intriguing possibilities around new therapies.
There's so much happening at Garvan, and so much of
it's driven by our younger researchers, um, which is, I think,
(26:14):
incredibly exciting and, and really does point to a bright
future for the Institute.
Dr Viviane Richter (26:18):
What about genomics?
Professor Benjamin Kile (26:19):
Genomics is one of our great strengths, and I think
the exciting thing about the genomics happening at Garvan at
the moment is we span everything from monogenic disorders, so
trying to understand rare diseases in single patients and in
single families, through to population genomics under Daniel MacArthur, trying
to understand and build out an atlas of human variation,
(26:39):
which will enable so much progress in enabling the application
of precision medicine ultimately in the healthcare system. But we're
also now, under Joseph Powell, drilling down into single cells
and how single genes are regulated in single cell types,
which is, uh, a hitherto, um, impossible task that Joseph's
now pulling apart and elucidating. That's important because it starts
(27:03):
to get at the, the nuance of complex human diseases
like cardiovascular disease, diabetes and others. So, the level of
sophistication and detail being applied there, I think is, it
is absolutely cutting edge and it's, it offers so many
possibilities to understanding how these diseases, which have been studied
for decades and studied at a genetic level for decades,
(27:23):
but it's still out of reach, I think that's an
incredibly exciting area.
Dr Viviane Richter (27:37):
With so much exciting research happening at Garvan, I think what really has struck me at my time at Garvan is the sense of community around the Institute. Have you felt the same way?
Professor Benjamin Kile (27:38):
I, I totally agree, Viv. It's been one of the
most exciting aspects for me coming to Garvan. Obviously, I
was well aware of Garvan, what it represents, the research,
the researchers, um, but I hadn't quite appreciated the place
it holds within the landscape in, in New South Wales and,
and the relationship it has with the community. We depend
on community support to do what we do. I've often said,
(28:00):
we turn public support into public knowledge, and ideally that
knowledge can then be translated into impacting patient lives. But
the degree to which Garvan is integrated into the community
and the level of support and the support that, in
some cases, some families goes back two or even three
generations has been a revelation to me. I've not seen
(28:23):
that before in, in Australia, so, realising what Garvan represents
to people has been a real thrill. Also creates a
real sense of obligation. You know, we're here, as I
keep saying, to make an impact, so the support that
we get really engenders in me and, I think, the
folks at Garvan, a sense of obligation to really deliver, and
we're gonna be increasingly focused on that in the decade
(28:44):
to come.
Dr Viviane Richter (28:45):
So what do you see as the key challenges for Garvan?
Professor Benjamin Kile (28:49):
I think the major challenge, Viv, is supporting the careers of
individual researchers. We've seen over the 27 years I've been
in medical research, the dissipation of, of many of the
career structures that used to be supported by funding agencies,
particularly in this country. You've seen the rise of, of
team science, of consortium science, and an increasing emphasis on
(29:10):
multi-disciplinary teams, etc. which is all wonderful. But it does
make it hard for individual researchers to sustain their careers.
And I think younger researchers looking upwards now really do
wonder how on earth they're gonna be able to fashion
a lifetime in research. And Garvan's challenge is to support
younger researchers, in particular, to enable them, to mentor them,
(29:33):
develop them. The system in Australia is radically underfunded. So
the financial sustainability challenge is ever-present, not just for supporting
individual researchers, but for developing the technology we need, um,
and supporting all the professional systems that, that make Garvan happen. So, ultimately,
it is a financial sustainability challenge.
Dr Viviane Richter (29:55):
Ben, if we dial back to 20 years ago, we
would have just witnessed the completion of the first human genome.
Say if we dial forward 20 years, what impact do
you think Garvan will have had?
Professor Benjamin Kile (30:09):
I see myriad opportunities, and I've talked about a few
aspects of the research that really excite me at the moment.
I think in autoimmune disease, our researchers talk about treating
patients with the right drug at the right time. Precision immunology,
if you will. And I, I think that is a,
a very real prospect. Great progress has been made in
cancer research in identifying the specific causes of a particular
(30:32):
patient's tumour and, and matching them with therapy. I think
we'll see that in autoimmune disease. I think within 20 years,
it is entirely conceivable that most, if not all, autoimmune
diseases will be treatable, if not ultimately cured. I think
Garvan has a big role to play there. If you
look at pancreatic cancer, I would hope that 20 years
from now, the enormous effort that Garvan is putting in
(30:55):
and the enormous talent that we have in that space
will have yielded massive differences in the ability to treat
pancreatic cancer. It is a very nasty disease. And I
think the, the level of technological sophistication we're bringing to
that space will ultimately yield major progress. On the genomic
side of things, there is no doubt that 20 years
from now, we will have, I think, nailed down the
(31:19):
genetic causes of every rare disease, and I think we'll
be making real progress in treating some of those diseases.
And on the complex genomic side of it, the sort
of single-cell approaches that people like Joseph Powell are developing,
I do think there will be different ways of treating
complex diseases that are, that we can't encapsulate at this point.
(31:39):
We just don't know what they are, but there's no
doubt that the nuance and sophistication of understanding those complex
diseases will be much, much further advanced, as will the
therapeutic advances. And I think Garvan should be looking back at,
as I've said, medicines that had their origins in Garvan science.
I was asked this question at a, at a staff
meeting recently, and it dawned on me after the event
(32:01):
that I think one of the things I'm most excited about,
and I wish I could travel forwards in time, are
the discoveries that I can't imagine that the folks at
Garvan can't imagine. The beautiful thing about science is it's unpredictability,
the serendipitous, the synergistic discoveries, and scientific progress is littered
with those moments. And I'm looking forward to two decades
(32:23):
of those at Garvan, just seeing what those discoveries are.
Those things that 50 years from now, people will say, oh,
that was discovered at Garvan. That concept, that idea, that possibility,
that happened at Garvan. To finish where I started up
makes the hair stand up on the back of my neck.
Dr Viviane Richter (32:39):
Ben, you lead a medical research institute of 700 staff.
What drives you day to day and how do you
inspire the people that work at Garvan?
Professor Benjamin Kile (32:49):
I hope to inspire the people who work at Garvan.
What drives me is, is the same thing that drove
me into doing an honors project in 1997, which is
the desire to make a difference. Obviously, I find science
invigorating and exciting, but it's the impact that science makes
that drives me, the impact of medical research. Watching over
(33:09):
27 years in, in my career, the, the progress that's
been made in, in different disease areas is, is just
absolutely phenomenal. And so I remain as excited about medical
research as I have ever been. And so it's not
hard to get motivated. I stand up and I talk
at Garvan about what we're doing and people sometimes comment,
"It all sounds authentic, Ben." And that's because I'm simply
(33:32):
saying what I think and what I feel. So getting
motivated is not hard, and I hope that, that, you know, enthusiasm,
that inspiration, um, does inspire Garvan people. What I find though,
is that across the Institute, whether it's the folks who
work on the front desk, whether it's the people in
the mouse house, the people on the finance team, the
people in the research labs, people in fundraising, wherever you look,
(33:54):
you find people who are innately motivated by the possibilities
of medical research, and by the possibilities of Garvan. I
don't have to inspire everyone who works at Garvan. I
don't have to inspire our supporters. I try, um, and
I try and bring them together and support them, but
that innate passion and enthusiasm for medical research and, and
(34:14):
progress in, in making a difference in patients' lives is
there in, in so many people at Garvan.
Dr Viviane Richter (34:20):
Professor Benjamin Kile, thank you so much for joining us
on Medical Minds.
Professor Benjamin Kile (34:25):
It's been an absolute pleasure. Thank you for having me.
Dr Viviane Richter (34:27):
If you'd like to know more about Garvan's research or
donate to the work we do, head to garvan.org.au. And
if you've enjoyed this podcast, please leave a review and
share with other podcast lovers. I'm Dr Viviane Richter. Thanks for listening. This podcast was recorded on the traditional Country of the Gadigal people of the Eora Nation. We recognise their continuing connection to land, waters and community. We pay our respects to Aboriginal and Torres Strait Islander cultures and Elders past, present and emerging.
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