Transcript

Basic bone science · 'Bone Up'

0:00
Hello and welcome to Bone Up, the podcast all
0:04
about bones, how we make them, why we break them
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and if we fully understand them. I'm David Armstrong.
0:11
Hi and I'm Richie Abel and over this series we're
0:15
going to be exploring osteoporosis, bones, what
0:18
we know and what we're yet to discover and we
0:21
hope you will join us on the journey. So for
0:24
anyone keen to learn more about our infrastructure
0:27
of calcified collagen, this is bone up so hello
0:55
and welcome to another episode of bone up the
0:58
podcast we are about, I suppose, halfway through
1:02
our second series, Richie, would that be right?
1:05
And a very exciting guest coming up today, which
1:07
we'll talk about later. How have things been
1:10
for you? Pretty good. Just got back from holiday,
1:13
so I'm nice and relaxed. And before going away
1:16
on holiday, I submitted a couple of grants to
1:19
UK government, and each of them took about nine
1:22
months to write. So it's been quite a year. I'm
1:27
looking forward to... start of the new academic
1:29
term. What have you been up to? How are preparations
1:34
going for the Royal Osteoporosis Society conference?
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Yeah, well, as you say, as well as my day job,
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I have the honour, I think, of being vice chair
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of the committee, which is arranging the... conference
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the Royal Osteoporosis Society conference September
1:51
13th and 14th of September in Manchester I think
1:54
the preparations are going well we've a really
1:56
exciting program we've lots of fantastic guests
2:00
from both inside and outside the UK um and uh
2:04
yeah it's it's it's we're starting to get excited
2:07
a little bit nervous but we're very excited about
2:10
it to see it all come together so um Certainly,
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if you're listening to this and you're still
2:15
in two minds, please do come along and join us
2:18
in Manchester and you might even get to meet
2:20
your two favourite bone podcasters. I'm genuinely
2:29
excited about the conference. In all honesty,
2:32
the Osteoporosis Society conferences are the
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best organised that I've ever been to. Everything
2:39
runs really smoothly. The food is good. The talks
2:42
are great. The audience are relaxed. Everybody's
2:45
learning a lot of useful stuff and it's really
2:47
good fun. And there's always, you know, some
2:49
drinks reception or dinner or something. It's
2:52
like I've met so many wonderful people going
2:54
to the meetings. Yeah, there's a lot of great
2:56
people connected with the charity and who work
3:00
for the charity and we've had great leadership.
3:03
It's a great charity to be involved with. As
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I think you know yourself, most people in the
3:07
world of bone and bone research seem to be fairly
3:10
friendly and collaborative. It's something we're
3:14
certainly looking forward to. We're not planning
3:16
to do a formal podcast from the conference this
3:22
time, but certainly do come up and say hello
3:25
if you're a listener. We'd be glad to get a selfie
3:29
with you, maybe. Yeah, it'd be lovely. It'd be
3:32
nice to get some feedback as well. So that sort
3:37
of brings us on to today and our special guest
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star, I sounded just like the Muppet show there,
3:43
I was going to say our very special guest star
3:45
for today is a well -known bone researcher from
3:49
Imperial College in London called Dr. Richie
3:52
Abel. You know, over the last couple of years,
3:57
both Richie and I have talked a little about
4:00
what we do. You've heard an interview with one
4:03
of my patients. I've talked about drugs I've
4:05
used in clinics and so on. And you've also heard
4:07
Richie talk a lot about the work that he does,
4:11
but really just in bits and pieces. And we thought
4:13
it would be really good if we sat down and did
4:15
a proper interview so you got an idea of just
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the depth and breadth of research that Richie's
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involved with. and just got a little bit of an
4:25
idea of the passion that he brings to to this
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work and uh and we decided just to do an interview
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where i would interview him like one of well
4:34
like one of our guests so um welcome richie to
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the podcast formally as a guest richie abel the
4:44
podcaster we know and love we sort of feel we
4:47
know a little about what you do during the day
4:49
but other than that you're a scientist and clearly
4:53
wear a white coat and goggles and are bent over
4:55
a test tube all day but tell us what is your
4:58
role actually involved with a sort of a typical
5:01
dr abel day from eight in the morning to whatever
5:05
time you work out at night thank you for that
5:08
lovely introduction yeah i guess i guess the
5:13
uh My mother's and the public's view of scientists
5:16
is that we wear white coats and work in labs
5:19
coming up with amazing discoveries that are going
5:21
to change the world. But in all honesty, the
5:24
job is mostly writing Word documents. I guess
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it's quite a diverse job to work in academia.
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Generally, day to day, there's a few important
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tasks I have to do. Primary one is supervising
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PhD students and postdocs. I have about nine.
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supervise or co -supervise and they take up a
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lot of my time. Each one's doing a piece of independent
5:47
research and they need help and support. As we
5:51
spoke about in the intro I spend a lot of time
5:53
writing grant applications. They can take a really
5:56
long time to write and we have to put in a few
5:58
every year. I do some work with companies, usually
6:03
tech companies who are trying to develop devices
6:06
for diagnostics for bone disease or maybe developing
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treatments for bone disease. And that's always
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really good and fun to do because it's hopefully
6:15
going to be quite impactful research. I do teaching.
6:19
Until recently, I ran the research skills course
6:22
on the medical degree at Imperial College, which
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was a lot of fun teaching undergraduate medical
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students how to do research. And Imperial College
6:32
is very focused on turning out clinical academics.
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Now I run the BSc in Surgery at Imperial College,
6:41
which is a really fun thing to do, teaching budding
6:45
surgeons how to do research in surgery. A big
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part of our job is public and professional engagement.
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We're all expected to be able to somehow engage
6:57
with the world about the work that we do in our
6:59
labs and at Imperial. I guess that's one of the
7:02
reasons why this podcast got started, and that's
7:05
my outlet for engagement. I think a lot of people
7:08
outside our world don't realise that you have
7:12
to apply for grants to get funding to do research.
7:16
You know, I think the perception sometimes is
7:18
that you work in a big university, the money
7:21
is just there, you come up with the ideas and
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the research happens. But so much of the work
7:26
is actually involved in persuading people to
7:28
give you money, because if the money's not there,
7:30
then people don't get employed, the research
7:34
doesn't happen. When you're writing those grants,
7:38
what's most important from your point of view?
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Is it how exciting the research is, the idea
7:45
you have is? Or is it how sort of impassioned
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you make the plea about the disease in itself?
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Or what have you learned about grant applications?
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Because I suspect many people listening to this
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just won't have any idea about doing that. That's
8:04
a very good question. And it's something I ask
8:06
myself almost every day. How do you write a grant
8:10
that's going to land with the reviewers and persuade
8:13
them to give you the money? I think the first
8:17
thing to remember is that the people who review
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your grants are your peers, other researchers
8:21
in your field. And I think the most important
8:25
thing that you have to get across is that your
8:27
research will be impactful in some way. You will
8:30
develop some new knowledge, some new skills.
8:34
some new opportunities which are going to be
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useful for somebody in the world you know in
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an ideal world you're testing a new drug that's
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going to cure a disease yeah maybe at the other
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end of the scale more the research i do you're
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looking at the physiological mechanisms behind
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a disease which somebody might be able to manipulate
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to create the cure to that disease Even if your
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work is very impactful, you still have to sell
9:04
it. You have to be able to explain what that
9:07
pathway to impact is going to be. What would
9:09
the steps after your research be to make it impactful
9:12
in the world in some way? And you also have to
9:16
bear in mind that sometimes these grant applications
9:18
are quite long. I've written grant applications
9:21
that go up to 120 pages. Now, somebody is going
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to read that and you have to make your grants.
9:29
interesting and exciting and easy to read otherwise
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the reviewers will never really get into it and
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won't know how impactful or exciting the research
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is the hardest thing about this job is writing
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the grants because it's a one -shot deal you
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know you write it and if you get rejected that's
9:48
it but you have been successful very successful
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i think in saying it in getting grants over the
9:56
last few years certainly to do a lot of exciting
9:58
work that hopefully we will hear about today
10:00
so i'm sure your course on how to write grants
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is one which should be oversubscribed although
10:07
you don't want to give away all your secrets
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clearly because it is a competitive field isn't
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it you are competing against your peers it's
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very competitive sometimes the funding rate is
10:20
one in a hundred If you're lucky, the funding
10:24
rate is one in 10. It is incredibly competitive
10:29
and you have to be able to come up with projects
10:31
that really stand out and are written well in
10:34
order to be able to get the funding. It's a tough
10:37
job. Is this something you always wanted to do,
10:41
Richie? I mean, I've said to you that I really
10:43
wanted to be an archaeologist and still hope
10:45
to be one one day. I'm just doing medicine to
10:48
sort of fill in. You always wanted to be a bone
10:53
researcher. What did you do before this or what
10:55
brought you to where you are now? Originally,
11:00
I wanted to be a paleontologist and my undergraduate
11:03
degree was in zoology and my postgraduate degree
11:07
was in paleontology, a master's and a PhD. Just
11:11
explain to us what paleontology is, because,
11:13
again, some people maybe aren't familiar with
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the term. paleontologists are people who study
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fossils and those fossils can be anything from
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a dinosaur up to and including an early human
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and when i was young i was quite interested in
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anthropology which is kind of the study of humans
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and i did my phd in something called physical
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anthropology which is the study of human evolution
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and you usually do that with bony remains and
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my phd was about the evolution of the pelvis
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and bipedalism in humans. And after I finished,
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I went to work at the Natural History Museum
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in London. I got a job in the mineralogy department
11:58
and I installed a CT scanner. And I used that
12:01
CT scanner to scan fossils in the collections
12:05
to do work with paleontologists. I also scanned
12:08
lots of other really interesting stuff like meteorites
12:10
from Mars, hammerhead sharks, insects encased
12:14
in amber, all sorts of things. I really enjoyed
12:17
doing that job. It was about studying the collections
12:20
in the Natural History Museum to try and unlock
12:23
the secrets of the universe and the planet Earth
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and the natural world around us. It was absolutely
12:29
amazing. So how did you move on from, if I can
12:32
call them, dead bones to living bones then? While
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I was at the museum, I started to support scientists
12:42
from Imperial College who were doing biomedical
12:44
research. They would come to the museum to use
12:48
the facilities. Listeners at home, you might
12:51
not know this, but the Natural History Museum
12:53
is actually a really big research institution.
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There are about 400 scientists and research staff,
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and I was one of them. And part of the research
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we did would be with universities all over the
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world. And we had lots of really amazing expertise.
13:07
Mine in particular was in imaging, using CT scanners,
13:10
etc. So I worked with people at Imperial College
13:13
who were designing stents, who were designing
13:16
implants for putting into humans to replace knees
13:20
and hips and that kind of thing. So I got an
13:23
introduction to the biomedical research that
13:25
was going on at Imperial College, and I was supporting
13:28
the scientists to scan medical devices and then
13:32
create 3D reconstructions, which they would use
13:35
in their research. And then one day... I saw
13:40
a job advert at Imperial College and they wanted
13:43
somebody who could use imaging to study bone
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diseases like osteoporosis. And I thought, wow,
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you know, I've been supporting the people at
13:52
the college who are doing this job. Maybe I could
13:54
do that job. But I didn't really know much about
13:57
osteoporosis. So I had a quick Google and I came
14:00
across what was then the National Osteoporosis
14:03
Society website. And they had a video, a testimony.
14:09
from somebody living with osteoporosis called
14:11
gary he was explaining that he suffered a vertebral
14:17
fracture and as a result of that vertebral fracture
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he lost his job working in packing in a factory
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and because he lost his job he lost his income
14:25
he lost his home and he lost his friends i was
14:29
really just moved by that story just the devastating
14:32
effect that a fracture would have on somebody's
14:35
life and i thought i'm gonna go for this So I
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applied for the job at Imperial and I've never
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really looked back. Wow, that's very interesting.
14:44
Again, it shows some of the passion you have
14:46
for this condition and for the work that you
14:49
do. And I think this is something we've talked
14:51
about before. People come from different areas
14:54
sometimes to bone research and probably actually
14:58
to work even clinically in bone. It's something
15:00
you've heard. me and other clinicians talk about
15:03
how, you know, some people come as endocrinologists,
15:05
some come as rheumatologists, some come as care
15:07
of the elderly physicians. And I think that quite
15:10
diverse background that people bring to bone
15:14
and bone health and bone research is a healthy
15:17
thing and a good thing because you bring in,
15:19
I mean, look at the experience you've had of
15:21
imaging fossils and all that, that you're still
15:23
working out in your projects. I think that's
15:25
a good and a healthy thing. I get the impression
15:28
you've chosen to be where you are now. You haven't
15:30
just sort of dropped into it, which is good.
15:34
I'm conscious of time here. I would like to ask
15:36
you about some of the projects you've been doing
15:38
that you've told us sort of little snippets about
15:40
in previous podcasts. And you can mention that
15:45
or not, but I presume most of these represent
15:47
successful grant applications. I mean, one of
15:51
the things that I find interesting when you mentioned
15:53
to me. You've done work with the Royal Ballet
15:56
Company. I have a small interest or an increasing
16:01
interest, I think, in stress fractures and injuries
16:05
in young athletes, particularly in female athletes.
16:08
I get some more referrals for that to my clinic.
16:11
Ballet dancers are a group of people who have
16:13
a lot of problem with stress fractures as well.
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They're amazing athletes. And that's something
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you looked at and maybe tried to learn things
16:22
about bones in general from what happens with
16:24
ballet dancers. Tell us a little bit about the
16:27
work that you did with the Royal Ballet Company,
16:30
if you would. A lot of projects in science come
16:34
from chance meetings and chance conversations,
16:36
you know, having a beer with someone. Way back
16:39
in about 2014, somebody was visiting the lab.
16:43
His name was Dr. Greg Retter. And he was a clinician
16:46
at the Royal Ballet Company in Covent Garden
16:48
in London. And he was being given a tour of the
16:51
lab. And we got talking about the research that
16:54
I was doing into osteoporotic fractures. And
16:58
at the time, I was studying some osteoporotic
17:00
stress fractures. And he said, well, you know,
17:02
our dancers get a lot of stress fractures. Do
17:06
you think you could apply the research that you
17:08
were doing on the ballet dancers? They needed
17:12
to know. who was going to who were going to get
17:15
stress fractures and the stress fractures normally
17:17
occur in the feet right they wanted to know how
17:21
they could try and speed up the healing of the
17:23
stress fractures and they wanted to know how
17:26
they could judge when a dancer who suffered a
17:28
fracture could return back to training and performance
17:30
and i was quite surprised really to to hear how
17:34
serious the injuries are a stress fracture as
17:38
you well know it's just a tiny fracture maybe
17:40
in a small bone in the foot But they can be enough
17:44
to put a dancer out of training and performance
17:46
for many months or a year. And in serious cases,
17:48
they can be career ending. I hit the literature,
17:52
which is the first thing you always have to do
17:54
as a scientist. And there wasn't really much
17:55
information about stress fractures in ballet
17:57
dancers other than they tend to have a lot. Yeah.
18:01
So we thought we need to try and do something
18:04
to study the natural history of stress fractures
18:07
to try and get some idea about which dancers
18:10
get them and when and how. So we ran two pilot
18:14
projects, about three months long each, down
18:17
at the ballet in Covent Garden. And what we tried
18:21
to do was see if it would be possible to recruit
18:25
a group of dancers into a study and follow them
18:28
over time to look at their lifestyle, to look
18:32
at their activity and to collect urine samples
18:36
and blood samples to analyse their physiology.
18:40
We were able to do that. The dancers are actually
18:43
very engaged in the research. They want to do
18:45
whatever they can to prevent themselves getting
18:47
stress fractures. I used the data to try and
18:51
understand how the dancers were living their
18:55
lives and how that could potentially be affecting
18:57
their risk of a stress fracture. And as you can
19:00
imagine, the first thing we discovered was that
19:02
dancers do an incredible amount of exercise.
19:06
One thing we tried to do as part of the study
19:08
was put pressure sensors in their dancing shoes
19:11
so that we could understand what kind of forces
19:14
were going through their feet, because maybe
19:16
bigger forces equal more stress fractures. The
19:19
forces were so big they broke all the pressure
19:21
sensors. They worked in football players and
19:25
rugby players, but ballet dancers broke them.
19:30
So the urine and blood samples actually turned
19:33
out to be very useful. and very insightful. The
19:38
other thing we found out was that when we measured
19:41
biomarkers for bone turnover in blood and urine,
19:46
the ballet dancers didn't really differ from
19:50
age and sex match controls. We've got a bunch
19:52
of controls from Imperial College who are basically
19:54
medical students. And we measured molecules in
19:59
the urine and blood that tell us how much bone
20:02
is being resorbed. and how much bone is being
20:05
formed. And I think they're the same markers
20:08
that you probably use in your clinical practice.
20:10
Yeah. P1NP for formation and CTX for resorption.
20:13
Exactly. I sent several of those this morning
20:16
just before I came to speak to you. So yeah.
20:18
So that's great to hear you're using things which
20:20
are relevant to me in the clinic. Yeah. Well,
20:23
yeah, exactly. And this is important because
20:25
if we are going to do something useful for the
20:27
dancers, it really does need to build into current
20:29
clinical practice. Absolutely. Yeah. What I found
20:34
was that the rates of remodeling, which are really
20:37
the rates of repair in bone, this is the removal
20:40
of old and damaged bone and replacement with
20:42
new healthy bone. The rates of repair in the
20:45
dancers were about the same as the controls,
20:47
even though they were doing just crazy amounts
20:50
of exercise. Ballet dancers make rugby players
20:54
and football players look lazy. So this is interesting.
20:59
Why is it that even though they do all this extra
21:02
activity, the bones can't seem to increase the
21:06
amount of repair to stop these stress injuries,
21:09
these stress fractures occurring. The other thing
21:12
that the urine and blood samples were useful
21:15
for was looking at estrogen levels. And estrogen
21:18
is a very important hormone for powering up bone
21:22
cells. It encourages osteoclasts and osteoblasts
21:25
to resorb and form bone. So I thought, well,
21:28
you know, maybe there's a difference in the estrogen
21:30
levels. When I compared the estrogen levels,
21:33
I found that the dancers were slightly lower
21:35
than the controls, but not much lower. And there's
21:38
lots of studies that have looked at other athletes
21:41
like, you know, runners and rowers, et cetera,
21:42
that show that women who exercise a lot have
21:46
lower estrogen levels. And that could affect
21:48
bone repair because the low estrogen might mean
21:52
that the bone cells aren't powered up enough
21:54
in order to be able to repair the bone. But there
21:56
wasn't that much of a difference. Perhaps a more
22:01
important factor could be the metabolism of the
22:03
oestrogen. I was able to use the urine samples
22:07
to look at how the oestrogen was metabolised
22:12
in the dancers' bodies. And as you well know,
22:16
oestrogen in the body is metabolised into lots
22:19
of different molecules. And it's those metabolites
22:22
that go to cells and react with the receptors
22:24
on the cells and give the cells some instruction.
22:28
And there's basically two kinds of metabolites
22:30
in the body. There's a 16OH version and a 2OH
22:35
version. Metabolism of estrogen is about hydroxylation,
22:39
which is the adding of an oxygen and hydrogen
22:42
to the molecule. The 16OH version of estrogen
22:47
binds very strongly to the receptors on cells,
22:51
and the 2OH version binds less strongly. And
22:56
what I found was that in the controls, estrogen
22:59
was mostly metabolized into the 16OH version,
23:03
the strong version. But in the dancers, estrogen
23:06
was metabolized into the 2OH version, the weak
23:09
version. It could be that there's an imbalance
23:13
in estrogen metabolism in the dancers that favors
23:18
the formation of metabolites, which don't have
23:21
a very strong effect on cells, including the
23:23
bone cells. Mm, that's, yeah, that's a very subtle
23:29
outcome. I wish people could see you moving your
23:33
hands as you talk about this to see just how,
23:35
do you know, how engaged you are. are in it and
23:39
how much you sort of believe in all this work
23:41
because it is it is and it's the sort of work
23:43
which as you say we've talked about this before
23:45
it's a very small group of people but actually
23:47
it potentially has implications for much much
23:50
larger groups of people so i mean for all these
23:54
things the body does this for a reason the body
23:56
is not producing as much useful strong efficacious
24:02
estrogen in this group of people so why Why not?
24:07
Is their BMI lower than average? Is their menstrual
24:12
cycle lower than average? Is the body trying
24:15
to prevent something else happening and the bones
24:18
are suffering as a result of that? What's your
24:22
hypothesis for your next grant then on this?
24:25
Why the body is behaving in this way? Because
24:27
there's got to be some, as you know, there's
24:29
got to be some logical way in which the body
24:31
is doing this. It's not deliberately harming
24:33
its own bones. It's got to be some other potential.
24:35
advantage i presume to this so that's a really
24:39
good question when you think about dancers i
24:43
guess for everybody the first thing you think
24:45
about is bmi and diet yeah so in terms of bmi
24:49
the the dancers some of them had the same bmi
24:54
as our control some of them had a lower bmi than
24:57
controls as you might expect potentially low
25:00
bmi means low body fat Body fat is used to produce
25:04
estrogen, especially the triglycerides. So potentially,
25:07
yes, the production of estrogen and the estrogen
25:11
metabolism could be affected by low BMI. But
25:15
as I said, not all of them had very low BMI.
25:18
So maybe that's not it. So next thing we thought
25:21
is maybe diet. For a long time, people have tried
25:24
to study diet in athletes by collecting diet
25:27
diaries. They're notoriously bad because people
25:29
can't remember what they've been eating. I tried
25:32
some new techniques using mass spectroscopy.
25:36
A colleague of mine at Imperial ran the urine
25:39
samples through a mass spectroscope. I was able
25:42
to look at exactly what the dancers were eating
25:46
week by week. Actually, the dancers' diet didn't
25:52
differ from the controls. Just to clarify that,
25:56
you look in the urine, you find metabolites in
25:58
the urine, and you then can use... algorithms
26:01
to work back and work out exactly what those
26:04
people were eating in the previous day or few
26:06
days or week in terms of carbohydrates fats and
26:08
so on that's that's the thinking behind that
26:11
yeah which is an amazing tool actually to have
26:13
isn't it for research oh it's absolutely incredible
26:16
it's really going to be transformative and for
26:19
you in the clinical practice at some point you're
26:21
going to be able to collect this data from people
26:23
and give them specific advice on how they might
26:26
change their diet in order to prevent fractures
26:30
And so what advice, here's the, you know, $64
26:32
,000 question, if anyone else uses that expression
26:35
any longer, what advice did you give the ballet
26:38
dancers? So we found then that maybe the diet
26:41
was actually the same as controls and they are
26:44
medical students and probably they're eating
26:47
quite well. It's quite an informed group of people.
26:51
I looked at their diet for the dancers in comparison
26:54
to the WHO diet scale, which is a measure of
26:56
how good a diet is. It's measured from 0 to 100
26:59
and 40. 0 being very bad, 100 being very good,
27:05
and 140 being amazing. Dancers all scored 90.
27:09
So I think maybe this might overturn the stereotype
27:12
that dancers are not eating well, which could
27:15
be important. And it's a small study, and they're
27:18
the most elite ballet dancers. So how generalizable
27:23
this is to other dancers, I'm not sure. It stands
27:26
to reason if you're training and performing six
27:29
days a week, probably got to be eating quite
27:32
well, right? Otherwise, you're not going to be
27:33
able to keep up with that. One of the nice things
27:38
about studying the dancers is that it's a really
27:42
good group of people who we can use for public
27:45
engagement further down the line. So if we think
27:48
about going out with advice, we're the dancers.
27:52
I'm not really sure what to say yet. Maybe what
27:55
we need is a bigger study and we need to investigate
27:58
this imbalance in estrogen a bit more closely
28:01
and see if it's possible to rebalance the estrogen.
28:06
And there might be ways of doing that with diet.
28:08
Lots of very dark green veg like broccoli, etc.
28:12
contains phytoestrogens, which could help metabolism.
28:16
Maybe having more calories could help. Maybe
28:19
changing the exercise patterns could help. We're
28:23
not sure. I've got funding for a four -year study
28:29
to do a long -term follow -up of dancers and
28:34
to really interrogate the natural history of
28:36
stress fractures. Really study in great detail
28:41
in a lot more dancers the physiology that underlies
28:44
the stress fractures and hopefully if we can
28:47
tease apart differences in physiology between
28:50
the people who get stress fractures versus the
28:52
people that don't, maybe we can understand what
28:54
the mechanisms are. And potentially then we'll
28:57
be able to suggest some intervention or some
28:59
change in lifestyle or diet. And hopefully, whatever
29:04
advice applies to the dancers will also apply
29:07
to the general public. Yeah, you can see obviously
29:10
groups of people who would benefit from that
29:12
in the general public and the people who come
29:15
to my clinics. That's very exciting. I want to
29:17
move on to another area, again, which we've heard
29:20
you talk about on the podcast. And we've seen
29:23
some of your exciting photographs on Twitter
29:26
as well. And that's the work you do at the Diamond
29:29
Light Source. I know we talked about paleontology
29:33
earlier, and I was going to say that's the study
29:35
of dinosaurs. I know it's not really, but...
29:37
But that's how people perceive it, which is obviously
29:40
a study of very big things. But really, you're
29:42
interested in the study of very small things.
29:44
Isn't that right? And a lot of the stuff we do,
29:48
you know, you look at something like a FRAC score,
29:50
which is trying to give an estimate of someone's
29:55
risk of fracture based on population sort of
29:58
level studies and so on. But you're looking at
30:01
this thing called the nanoscale, which is how
30:04
bones break at way, way smaller than the width
30:07
of a human hair. Isn't that right? Tell us a
30:10
little about what you're investigating with this
30:12
diamond light source and how that all fits into
30:14
this interest in bones at a very, very tiny level.
30:19
And you can say something about dinosaurs as
30:21
well, if you like. Dinosaurs actually come in
30:25
here, and I'll tell you why in a second. They
30:26
always do. When it comes to bone, we as a community,
30:33
we know a lot about how bones work and fracture
30:36
at the whole bone scale, at the micro scale and
30:42
even the sub micro scale. But we know almost
30:44
nothing about bone at the nano scale and the
30:48
molecular scale. And we don't really know how
30:50
bones fracture at that level. You'd think it
30:53
would be important. If you ask a material scientist,
30:57
they'll tell you that when they're trying to
30:58
build a new material or build an item out of
31:01
a material, that knowing what the fundamental
31:04
building blocks are and how they fix together
31:06
and how they behave under load are really important
31:09
for understanding how the material is going to
31:11
behave. So you think it would be the same for
31:13
bone, but nobody's really studied bone at this
31:16
level. To just explain to the listener what we're
31:19
talking about here, at the nanoscale, bone is
31:22
made up of elastic collagen, which are stiffened
31:27
by calcium mineral nanocrystals. The analogy
31:33
that I would give, and I apologize, this is a
31:35
horrible one, is a sweaty sock. Cotton fibers,
31:40
elastic cotton fibers, when they are hardened
31:43
by salt crystals, can turn a floppy sock into
31:46
something as stiff as cardboard. Bone is basically
31:50
the same, right? It's these elastic fibers stiffened
31:53
by crystals. Only the organization is much better.
31:57
So you can have a bone that is basically 10 times
32:00
stronger than concrete, weight for weight. Very
32:04
few people have studied bone at this level. And
32:07
I think the main reason is because these structures
32:09
are so tiny, they're really hard to image, they're
32:11
really hard to measure. And to put this in perspective,
32:15
listener at home, imagine an object the size
32:18
of the sun, shrink it down to the size of a football.
32:22
and then shrink it down by the same amount again.
32:25
What you've got is one nanometer and that's the
32:27
size of a glucose molecule. I was kind of fishing
32:33
around for a way to study bone at this level
32:36
and it turns out there's only one technique and
32:38
that's to use a particle accelerator. Most people
32:43
will know about CERN which is a particle accelerator.
32:46
We have a similar one in the UK. It's called
32:49
the Diamond Light Source. It's in Didcot in Oxfordshire.
32:54
It's basically a giant steel donut about 560
32:58
metres around that accelerates electrons up to
33:02
near light speed and then bends those electrons
33:05
with magnets in order to create X -rays. As the
33:10
beam is bent, the electrons lose energy. It's
33:13
released in the form of an X -ray. And you can
33:15
use those X -rays to do really accurate... and
33:18
high resolution imaging of objects. And an interesting
33:23
thing to say here is that those of you who are
33:26
fans of Einstein will know that as things travel
33:31
faster, time for them slows. So these electrons
33:35
are traveling around in the synchrotron, right,
33:37
at near light speed, which means time for them
33:40
slows. What is a few seconds to us and an experimental
33:44
hutch is years. in the perspective of an electron
33:49
and yet we're using those to create x -rays in
33:54
our own time and i've never really been able
33:57
to put those two things together it's hard to
34:01
get your head around almost isn't it even that
34:03
concept of something you know something the size
34:05
of the sun shrinking to a football and shrinking
34:08
to the same amount of again i think the human
34:10
mind struggles almost to deal to deal with that
34:13
and i've always found that concept of time moving
34:15
more slowly as you speed up I think we all find
34:18
that difficult to do, but here you are being
34:20
able to use that to study bone. So tell me then,
34:24
what sort of questions are you asking? Let me
34:28
put it like that. What questions are you asking
34:30
that being able to produce the x -rays and the
34:34
x -rays in a way you can control? What questions
34:37
are you asking with those x -rays? So I want
34:41
to know, how is it exactly that calcium mineral
34:44
makes bones strong? I'm sure you're always telling
34:49
your patients to drink more milk, consume more
34:51
calcium. The listeners at home are probably hearing
34:53
about eating calcium, taking collagen supplements,
34:57
et cetera, to improve their bone quality. But
35:00
we don't really know how calcium makes bones
35:04
strong. The mineral crystals are a million times
35:09
smaller than your thigh bone. How is it that
35:12
such tiny crystals can make such a big bone so
35:15
strong? And really the fundamental interaction,
35:21
I think, in bone is the one between collagen
35:23
and mineral. I wanted to know how it is that
35:27
collagen is stiffened and made strong by nano
35:32
-sized calcium crystals. And I spoke to a colleague
35:36
of mine who worked at Diamond. He was actually
35:39
a paleontologist and he was studying fossil spiders.
35:44
And he said to me... There's a facility called
35:48
Diamond that might work for you. I'll put you
35:50
in touch. And he even helped me write my first
35:53
application to Diamond. I took a bunch of bone
35:58
samples from the hips of donor patients. I put
36:04
them into a beam line at Diamond. I measured
36:08
how the collagen and mineral nanostructures behave
36:12
when you load a bone sample. And what I discovered
36:15
is this. The first thing that happens when a
36:18
bone sample breaks under load is that the collagen
36:21
and mineral separate. So if you think about this,
36:26
a fracture in a bone starts when collagen fibers
36:32
and mineral crystals start to come apart. So
36:35
you can imagine if somebody falls over on their
36:37
hip and they break their hip. The hip is going
36:41
to begin by bending, right? The thigh bone is
36:43
going to bend. And that's going to pass stress
36:46
all the way down to these nanoscale building
36:48
blocks, the collagen and mineral. They're glued
36:51
together somehow. And if you put enough energy
36:54
in, they're going to break apart. That is going
36:58
to form a molecular size, then nano size crack,
37:02
which is going to propagate all the way through
37:04
the bone and break the bone. Yeah, so it's the...
37:09
It's the crystals are sort of not peeling off
37:12
the collagen. That's maybe not a good way to
37:14
put it, but that's sort of the idea. They're
37:16
coming off, is that? I think that's a really
37:18
good way to put it. Is that right? Because, you
37:20
know, our perception, let's say I get twin sisters
37:23
age 75 and they both fall over at the same time
37:26
and they both land on the right hip and one of
37:29
them breaks a hip and one of them doesn't break
37:30
a hip. And, you know, you do see this sort of
37:32
thing a lot and people say to me, why did I break
37:34
my hip and why did my sister not? Why did I fall
37:37
last month and break my hip and I fell in the
37:39
same place in the same way this month and I did
37:42
break my hip? And when you go obviously at something
37:44
at that nanoscale level, something happened when
37:48
the force that was applied through the bone at
37:50
a certain angle in a certain place. On one occasion,
37:53
there was enough elasticity or density in the
37:56
bone for it not to break. On another occasion,
37:58
it did break. And what you're saying to me is
38:01
it's maybe not all the collagen fibrils tearing
38:03
apart, but it's actually the first thing that
38:06
happens is the crystals actually peel off the
38:08
collagen. Now, I can't immediately tell you how
38:12
that's going to change my clinic next Tuesday,
38:14
but that's very interesting to me to feel we're
38:18
getting at some level of why bones actually break
38:21
in certain circumstances. Your line of thinking
38:26
there. is exactly the line of thinking that i
38:29
then had could this help us understand why some
38:32
people fracture and some people don't why is
38:34
it some people age healthily while others age
38:37
and fracture to try and interrogate this i took
38:42
two sets of samples one from the hips of people
38:45
who'd aged healthily without having a fracture
38:47
and one from people who'd aged and sustained
38:50
a hip fracture And when I loaded the bone samples
38:54
from those two groups, I found something very
38:56
interesting. In the group that had suffered a
38:58
fracture, the collagen and mineral came apart
39:02
at much lower loads. The mineral peeled off the
39:06
collagen at much lower loads, about a third lower.
39:11
Maybe if it's easier for a fracture to start
39:14
in the bone tissue, if it's easier for a crack
39:16
to initiate and begin and then propagate through
39:19
the bone, that could help explain, why those
39:23
fracture patients fractured and to take it a
39:27
bit further the sample that I used ranged in
39:31
age from about 45 years up to about 96 years
39:34
and what I found was is as people get older the
39:39
amount of force it takes to pull the collagen
39:41
and mineral apart decreases and it decreases
39:45
much more rapidly in the people who go on to
39:48
have a fracture So that's almost like a biological
39:52
bone age then. Is that a way to describe that,
39:54
that you could, if there were some way to examine
39:58
this in patients? Obviously, you're putting pieces
40:01
of bone into the synchrotron. My patients wouldn't
40:04
fit into the synchrotron and they still want
40:06
to hold on to their bones. But if there was some
40:08
way to measure that, you would be able to say,
40:11
you'd be able to spot the patients whose bone
40:13
was almost biologically older or something, is
40:16
that? I think it's a test you need that you can
40:20
do without putting pieces of bone into your diamond
40:23
light source. I kind of imagine that some people
40:29
fracture because they lose bone mass. And some
40:34
people fracture because they lose bone quality.
40:36
Bone quality being, you know, the quality of
40:39
the bone material. The diagnostics we have at
40:44
the minute, like DEXA. really focus on the bone
40:49
mass and partly bone quality because they measure
40:53
the mineral, but they don't take into account
40:55
the collagen and they don't take into account
40:58
the interaction between collagen and mineral.
41:00
So maybe if we could measure that, we would be
41:04
able to identify more people at risk of a fracture.
41:07
The difficulty we have now then is trying to
41:10
collect a measure of bone quality that can go
41:15
with the measure of bone. quantity. And before
41:18
we can do that, we have to work out what it is
41:21
exactly that glues the collagen and the mineral
41:23
together. And the honest answer is we don't know.
41:27
Bone community does not know what binds collagen
41:30
and mineral together. There are some theories,
41:33
and at the minute we're trying to test those.
41:36
And the way that I'm doing that is by using computer
41:39
modelling. I've reached out to the mechanical
41:42
engineering department and the chemistry department
41:44
at Imperial. They do something called atomistic
41:47
dynamic molecular modeling, where they study
41:51
how materials behave at an atomic level by building
41:54
models of them on a computer. And together we
41:57
have built a computer model of mineralized collagen.
42:01
And we are using it to try and work out what
42:08
exactly the nature of the bond between the collagen
42:11
and mineral is. And that could be useful for
42:13
two things. First of all, we could measure it
42:15
as a diagnostic for bone disease. And secondly,
42:18
it could be a treatment target for bone disease.
42:21
Yeah, because all clinicians involved in this
42:24
area have a small group of patients who do suffer
42:27
recurrent fractures, and yet their bone density
42:31
appears to be normal, basically. Yeah. And there's
42:34
sometimes other reasons for that. But there are
42:37
a group of people, often in their 40s and 50s,
42:39
who have hip fractures, who have wrist fractures,
42:42
who look in every way like a typical osteoporosis
42:45
sort of phenotype, but appear to have normal
42:49
bone density. So what I would really, and we
42:52
do things, you know, we sometimes measure bone
42:53
turnover, and it's much the same, and we go through
42:55
family history and maybe talk about menopause.
42:58
But really, we're not, you know, we're not in
43:01
a position. to give an explanation for it. So
43:05
that could be, they could perhaps genetically,
43:08
family history somehow, have a problem with whatever,
43:12
I'm going to say protein, it might not be a protein,
43:15
most things are proteins, is involved in basically
43:18
sticking the calcium crystal to the collagen.
43:23
And I suppose it strikes me when you're looking
43:26
at these people, have you thought of dividing
43:27
them up into those, for example, who have a very
43:30
strong family history and those who don't? Those
43:32
who are heavy smokers, for example, we know tend
43:35
to fracture more easily than those who aren't
43:37
heavy smokers. Are there other ways we could
43:39
look at what might be involved in that bond by
43:42
looking in the clinical area, you know, by looking
43:45
at dividing people into different sort of clinical
43:48
groups that I see? People who've taken steroids
43:51
and people who haven't. Do steroids affect that
43:53
bond, for example? So I have that data from the
43:56
donors and I have DEXA scans. So I know the BMD
44:00
and I know the T -score in the hip. We're just
44:04
crunching that data now and I'm trying to understand
44:07
how it is that loss of BMD might affect the bond
44:13
between the collagen and the mineral. And I suspect
44:17
basically if you're losing mineral, then there's
44:20
going to be a smaller surface area. As a result,
44:26
the region, the size of the area for bonding
44:29
with the collagen is going to decrease. So it
44:31
could be something simple like that. But then
44:34
you've got to think about the nature of the change
44:36
in mineral. When people lose bone mineral density
44:39
with age, we don't really know whether it's a
44:41
loss of mineral crystals, or a loss in size of
44:44
mineral crystals, or some combination of the
44:47
two. Depending on how the mineral is lost, could
44:51
have very different outcomes for a patient. I
44:54
remember a little while ago, you put a picture
44:56
on Twitter of a lady, I think she had a T score
44:58
of minus five. and yet had never suffered a fracture
45:01
yeah that you were just describing a situation
45:04
there well okay you've got people with normal
45:06
bmd but they fractured maybe several times why
45:09
maybe the flip side is how is it you can have
45:12
somebody who's got very little bone and they
45:15
don't fracture maybe it's very good material
45:17
i think your idea is a really good one if we
45:21
compare people with different bmds and look at
45:25
the structures and the mechanics at the nano
45:29
level we might be able to understand and tease
45:32
out these differences between quality and quantity
45:35
the difficulty that we have is that we're always
45:39
going to be limited in the number of samples
45:41
we can study because time at synchrotron is very
45:44
limited and there's no other technique that we
45:46
can use i'm hoping that computer modeling is
45:50
going to allow us to ask and answer these questions
45:52
and that once we've built a very good model of
45:55
bone that we'll be able to start modeling okay
45:58
what happens if you change the mineral density
46:00
what happens if you change the structure of the
46:02
collagen what happens if you change the alignment
46:04
of the collagen and then we'll be able to start
46:07
understanding how the system is changed by disease
46:10
yeah how it is that mass and quantity versus
46:18
quality affect the bone and then hopefully hopefully
46:22
we can pick up the signals which you might then
46:24
find useful in your clinical practice. You and
46:27
I would have to work together, dream up some
46:30
way of measuring these things in clinical practice.
46:33
That's what I was going to ask you. That's one
46:34
of the advantages of this sort of podcast. So
46:37
this isn't something you're writing down and
46:39
giving references for or putting in a grant application.
46:45
If I just say to you, let's imagine in 10 or
46:47
15 years time, as well as the DEXA scanner in
46:51
the room to the left of my clinic, which measures
46:54
bone density, bone mineral density. I have a
46:57
scanner or a machine of some sort in the room
47:00
to the right of my clinic, which measures bone
47:02
quality, and I'm able to put those together for
47:05
a patient. So what do I need to get the technician's
47:09
training in now? What is the bone quality machine?
47:12
I know that's sort of a very... cartoon -like
47:15
question, but what is the bone quality machine
47:18
going to look like? Do you think in practical
47:21
terms, is it a blood test? Is it a machine? What
47:23
is it? Off the record, just you and me listening,
47:27
Richie. So that's a really good question. And
47:31
I have been working with companies who are trying
47:33
to develop devices that can measure quality.
47:38
One was ultrasound. ultrasound is used in a lot
47:42
of industrial applications for example spotting
47:45
cracks in pipes and if you pass an ultrasound
47:49
wave up and down a bone it's possible to not
47:52
only measure the structure of the bone but also
47:55
the material properties because they affect the
47:58
speed of the signal the devices I've tested so
48:02
far didn't work very well because they couldn't
48:05
get enough signal through the muscle and skin
48:09
into the bone and back again to really measure
48:12
the quality of the bone there might be some ways
48:18
around that but ultrasound i think is possibly
48:21
the most likely way that we're going to be able
48:23
to get these measures in clinical practice and
48:25
it would do the same job as dexa for quantity
48:29
as well as getting the quality measure yes i
48:31
was going to say so what are you measuring in
48:33
quality with the ultrasound there is it the Is
48:36
it the flexibility of the bone, the elasticity
48:39
of the bone, or is it the architecture of the
48:42
bone at a microscopic level that we're not picking
48:44
up? What is the thing you're trying to measure?
48:49
Strength and stiffness. Okay. Strength is the
48:53
ability to resist fracture, and stiffness is
48:55
the ability to resist deformation. Okay, so the
48:58
way the sound waves travel through the bone,
49:00
you'll be able to tell how... stiff it is and
49:03
also how strong it is that's the idea as well
49:07
as just telling how much bone there is there
49:08
in ex vivo tests which is where we took bone
49:14
out of people and did the ultrasound we could
49:18
measure stiffness and strength pretty accurately
49:22
but when we try and do it in the body the measures
49:26
are not very accurate because the sound waves
49:29
are dissipated by The soft tissues. Yeah. It's
49:33
a lot wetter in the body as well, isn't it? Exactly.
49:36
And if you think about the hip, there's a lot
49:39
of soft tissue. You've got the bum. Absolutely.
49:41
And you've got the thigh muscles. They're really
49:43
big. So it's really hard to do. We have some
49:46
ideas about how to get around that, that we're
49:50
trying to work on. Another potential technique
49:53
is laser spectroscopy. There are some groups
49:56
that have developed lasers that you can shine
49:58
through the skin into the bone. And the laser
50:01
energy makes molecules in the tissue vibrate.
50:05
You can read those vibrations back and you can
50:08
study the chemistry of the bone. That could be
50:11
a nice way to maybe study the collagen and the
50:15
mineral and how well they're bound together and
50:17
what the nature of the chemical interactions
50:19
is. Very good. That's a very honest answer. We
50:23
promised ourselves we'd keep within time because
50:26
we tried to do this once before and just talk
50:28
for hours and hours, as you know. There's one
50:30
other thing which you've talked to me about recently
50:33
and I can see that sort of twinkle in your eye
50:35
more and more each time you talk about it. And
50:38
that's the relationship between environmental
50:40
pollution and bones, which is a fascinating area.
50:44
Many people will be aware, obviously, that, for
50:47
example, lungs can be damaged with environmental
50:49
pollution, with gases. People will be aware that,
50:52
for example, lead in the atmosphere can affect
50:56
the development of children, of brain development.
51:00
But is it true that environmental pollution can
51:03
affect bone health, can affect osteoporosis,
51:07
fracture risk? Fill in the gaps in that a little
51:11
and tell us what you're hoping possibly to look
51:14
at in that area and what we should be worried
51:16
about. I'm trying to find out if environmental
51:20
pollution can affect bone health, can damage
51:24
bone health. And we were talking about grants
51:26
earlier on and how difficult it is to write grants.
51:29
And you asked a very good question earlier. What
51:31
is it that you need to say? What do you need
51:33
to put down in order to get the grant? One of
51:35
the key things, I suppose, is being zeitgeisty.
51:40
The world has problems. And if you are targeting
51:42
your research to a problem, then you're more
51:44
likely to get the money. I have heard a lot about
51:48
how pollution affects organs in the body like
51:51
heart and lungs. And I thought, I wonder if it
51:52
affects bone. I hit the internet and read some
51:56
papers and there's a lot of epidemiological data,
51:58
that is studies of populations, which shows that
52:03
people who live in areas with very high levels
52:06
of air pollution are much more likely to suffer
52:11
from osteoporosis or go to hospital with a fracture
52:14
than people who live in areas with very low pollution.
52:18
Isn't that fascinating and something that a lot
52:21
of people don't know? I know it's incredible,
52:24
isn't it? The strength of the association is
52:27
very high. A paper in the Lancet, a review, suggested
52:32
that maybe air pollution can increase the risk
52:35
of a fracture by about 10%. And that maybe exposure
52:38
to air pollution could account for 10 % of fractures,
52:41
which is a huge amount. Some people will, of
52:44
course, say, well, is that a causation? Or is
52:48
that, are you just mapping people who... come
52:51
from lower socioeconomic backgrounds and live
52:54
in areas maybe where there's more pollution about
52:56
and maybe don't have as much disposable income
52:58
for food and exercise. What makes you think it's
53:01
specifically the air pollution? Where's the pathophysiology
53:04
behind this? You're absolutely right. Epidemiology
53:10
alone cannot prove that there's a cause and effect
53:12
relationship. If there's a very strong association,
53:15
it can suggest a cause and effect relationship,
53:18
but there's no guarantee. There was a call by
53:22
an organisation called the UK Clean Air Programme.
53:25
They wrote a report in 2020 saying that they
53:28
needed more people from engineering, biology,
53:31
chemistry, etc. to move into the air pollution
53:34
field to support research into studying the mechanisms
53:38
that underlie these relationships between pollution
53:43
and poor health. Because you need the epidemiology
53:46
and the mechanism combined as a stepping stone
53:49
to prove cause and effect. And it's only when
53:51
you can really prove cause and effect that policymakers
53:54
are going to take interest. Healthcare, environmental
53:57
policy, etc. So I'm trying to fill that mechanistic
54:01
gap. There's a few ways in which I'm trying to
54:04
do that. One way is by studying wild animals.
54:08
I've teamed up with some people at the Institute
54:12
of Zoology at London Zoo. They're studying the
54:15
effect of air pollution on squirrels. They're
54:17
collecting squirrels from central London along
54:21
a pollution gradient out through London and Richmond
54:24
and into Berkshire. They've given me the bones
54:27
and I'm looking at the bones to see if the squirrels
54:31
that live in central London have more particles
54:36
of pollution in their bone and whether or not
54:40
that's associated with weakness. And I'm doing
54:43
the same thing using a laboratory study. I have
54:45
collaborators in Australia at the Sydney Technology
54:48
Institute who've done an exposure study in mice.
54:52
They collected roadside pollution from a busy
54:57
road in Sydney in an air compressor. Then they
55:01
filtered out the particulate matter and they
55:04
dosed that to exposed mice and control mice in
55:07
a lab. And again, they were studying the heart
55:10
and the lungs, but they've given me the bones.
55:11
Wow. I'm going to be able to use those bones.
55:15
to study how pollution affects the bone. And
55:20
I think that maybe what happens is this. The
55:23
particulate matter in air pollution, especially
55:26
from roadside pollution, contains a lot of heavy
55:29
metals. Cars have a lot of wear in the engines
55:32
and the brake pads and the tyres, and there's
55:34
a lot of road wear. And that wear releases heavy
55:38
metal ions, magnesium, zinc, lead, etc. They
55:44
are very similar to calcium. When they are inhaled
55:47
or ingested into the body, they travel through
55:49
the blood supply to the bones where it seems
55:53
they replace calcium. I'm going to study what
55:57
happens in the bones when you replace calcium
56:00
with heavy metals. And it could be structural.
56:03
It could be that if you change the constituent
56:07
of the mineral, you change the glue with the
56:10
collagen. So maybe you can make it easier for
56:13
fractures to initiate. I'm also going to look
56:17
at cell biology because potentially once you've
56:19
got air pollution inside the bone, as the osteoclasts
56:22
and osteoblasts remodel the bone, like we were
56:25
talking about with the ballet dancers earlier
56:26
on, they might be affected by the pollution and
56:30
their cellular activity could be affected. And
56:32
we know osteoporosis is an imbalance in cellular
56:35
activity. Too much resorption, not enough formation,
56:39
maybe heavy metals. accelerate or potentiate
56:42
that effect. So there's a lot to think about
56:45
here. That's a very thorough answer to the question
56:49
about pathophysiology. I think we'll all be very
56:52
excited to see how that goes. And yeah, that's
56:56
very interesting. Richie, we've worked together
56:59
for a few years now. It's been an enormous pleasure
57:02
for me to work with you. You bring a huge passion
57:06
to everything you do. clearly at work you bring
57:10
a huge passion to being a dad as well i can see
57:12
um are you happy with your career up to now and
57:17
what would you still like to achieve let me just
57:19
let me just put it down what would you still
57:21
like to achieve in your in your career i think
57:28
i am happy i get to do quite a broad range of
57:32
projects which keeps me interested i've got uh
57:37
visit places and people that maybe most people
57:41
don't ever get to go to when we were getting
57:44
the ballet research started i got invited to
57:46
go down to the royal ballet in covent garden
57:48
and i got a behind the scenes tour and it just
57:51
blew me away this is absolutely fantastic place
57:54
and i remember there was a press show and i got
57:58
to sit in a box and watch the press show for
58:00
the ballet how many people get to do things like
58:02
that in terms of what would i like to achieve
58:07
I would like to do a piece of research and collect
58:10
some evidence that's going to change healthcare
58:13
or environmental policy. I'd like to do something
58:18
really good that would change the way people
58:22
live their lives and make their lives better.
58:26
And potentially to do that, maybe one day I could...
58:31
Also move out of a research career and go and
58:34
work for a government body or a think tank that
58:36
works on developing policy. Potential ambition
58:41
of mine one day. Wow. I'm sure, Richie, you would
58:44
bring a fantastic amount to anything you were
58:47
involved with. As I said, it's been a great pleasure
58:50
to work with you and to do these podcasts with
58:52
you. And we promised ourselves we would do this
58:55
in under an hour and we're coming up to just
58:57
59 and a half minutes. So maybe you get a chance
59:01
to go home tonight as well, a little earlier
59:04
and see your son as well. Because I think you've
59:08
been inspiration to him. Oh, thanks, David. I
59:13
really enjoy doing these podcasts with you as
59:15
well. I've learned so much and got so much more
59:17
insight and it's been such a... It's been such
59:19
a fun thing to do. You know, it's kind of one
59:22
of the highlights of my week now. That's great.
59:25
Something I think we really enjoy listeners and
59:29
we're getting great feedback and we hopefully
59:30
will continue to do these as long as people enjoy
59:33
listening to us. So we'll get to meet up face
59:36
to face again, Richie, in a few weeks time in
59:38
Manchester, which will be great. And until then,
59:43
I think we just draw things to a close for today.
59:47
Thank you. Bye bye, everyone. Thanks very much,
59:51
Richie, for your interview today. Bye now.