Dr Rich Scott and Adam Clatworthy: Reflecting on 2024 - A year of change and discovery

As 2024 comes to a close, we take a moment to reflect on what has
been a busy year at Genomics England and in the wider genomics
community. Throughout the year, guests have joined us to discuss
groundbreaking research discoveries, important ethical
considerations, and share their personal stories. It was also a
year of transformation: we rebranded our podcast as Behind the
Genes, welcomed Dr Rich Scott as our new Chief Executive Officer,
and launched the Generation Study, in partnership with NHS
England. The Participant Panel also saw changes, with Kirsty
Irvine stepping into the role of Chair and Adam Clatworthy and
Helen White becoming Vice Chairs.


In this special end of year episode, Adam Clatworthy, Vice-Chair
of the Participant Panel, sits down with Dr. Rich Scott, CEO of
Genomics England, to look back on the highlights of 2024.
Together, they revisit key podcast moments, reflect on research
discoveries, and share insights into the evolving world of
genomics.


Below are the links to the podcasts mentioned in this episode, in
order of appearance:


Celebrating genomic breakthroughs - Insights from the
Festival of Genomics

Shining a light on rare conditions

How has a groundbreaking genomic discovery impacted thousands
worldwide?

How can we work in partnership towards a new era of genomic
medicine and research?

How has design research shaped the Generation Study?

How can we bridge the gap between diverse communities?

Can Artificial Intelligence accelerate the impact of
genomics?



"It's really important that we just continue to bring that
patient and participant community on that journey, just to ensure
that they really understand the full benefits. And we've talked
about that on the episode today. I know that the panel has always
encouraged the Genomics England team to look at its boots while
shooting for the moon. I really like that phrase just to make
sure, look, we can't forget where we've come from to make sure
we're taking people on that journey"


You can download the transcript or read it below.


Adam: Welcome to Behind the Genes. 


Rich: Our vision at Genomics England is a world where everyone
can benefit from genomic healthcare, thinking about how we ensure
the lessons we’ve learnt through our diverse data programme is
embedded across all of our work.  So that word “everyone”
applies to people in lots of different ways, different
communities people come from, different socioeconomic
backgrounds, making sure that equity is baked into all of our
work.  And there’s real opportunity for genomics to play a
broader role than in rare conditions and in cancer, we’re proud
of the impact we’re already having there, and we should really
look to the future. 


Adam: My name is Adam Clatworthy, and I’m the Vice-Chair for rare
conditions on the Participant Panel at Genomics England.  On
today’s episode, I’m going to be joined by Rich Scott, CEO of
Genomics England.  We’re going to be taking a look back at
the key milestones from 2024 for Genomics England, and really
discussing our hopes and aspirations for the year ahead. 
During this episode we’ll also hear from some of our guests we’ve
had on the show this year, who have helped shape our discussions
and shared some of their most impactful moments and
insights.  And if you’d like to listen to more like this,
then please subscribe to Behind the Genes on your favourite
podcast app.  So, with that, thanks for joining me, Rich,
how are you doing? 


Rich: I’m great, thanks for hosting today, I’m really excited
about it.   


Adam: So, Rich, it’s been a pretty exciting year for you, you’ve
taken on the CEO role at Genomics England full-time, so why don’t
you just start by telling us about how those first few months
have been for you? 


Rich: It’s been a really exciting year, I think for us overall at
Genomics England, and obviously personally taking on the CEO
role, which is an enormous privilege.  I’ve been at Genomics
England nine years, and I think both a privilege and a real
responsibility to take on the role.  To think both about how
we continue to honour the commitments we’ve given our
participants and those we work with, and to think about the
future, where we might go together, what evidence we need to
generate, what our systems need to support.  So it’s been
great taking on the role, and thinking about that, both the
present and the future, and there’s been lots, as we’ll talk
about, there’s been lots going on. 


Adam: No, that’s great.  And I must say for myself as well,
I started the Vice-Chair role at a very similar time to you early
in the year.  When I started, we were in the process of
looking for our next Chair.  Obviously, we had Jillian and
Rebecca, both standing down, after many years in the role. 
They’ve been there from the start, really guiding the Panel
through this amazingly successful period.  But for me, I’ve
really enjoyed working in partnership with Helen, who is our
Vice-Chair for cancer.  It’s been a real partnership, in
terms of filling in for that interim leadership role.  And
we wanted to make sure that we weren’t just caretakers, we were
really continuing to be actively involved in a lot of the
discussions that are happening with your colleagues across
Genomics England.  Very much leading the Panel, and starting
to have those important discussions around, where does the Panel
go next?  And what’s our strategy for the next two to three
years?  What are the key areas that we can drive real value
and impact, in line with your own milestones at Genomics
England?   


And, of course, I’ve just loved getting stuck into chairing the
Panel meetings as well, for me, that’s the best part, is really
bringing together these amazingly diverse and passionate
people.  With so many different personalities, lived
experiences, and a combined passion for just taking this forward
together, and making sure that the benefits of genomics really
impact, and that’s felt by the wider community itself.  So
there’s been lots of highlights to recognise this year, a real
stand-out for me has to be the Genomics England Research Summit,
from what I understand it was the most attended event to
date.  And it was just so good to see that a lot of the
Panel were front and centre across that event, sharing their
stories, having a really active role, whether introducing
speakers, or telling their own journeys as part of the Q&A
sessions.  


I myself was really privileged to be on stage with Baroness
Nicola Blackwood, literally nine days after I officially started
the role.  So it was great to just dive in at the deep end,
get in front of an incredible audience, and just see that the
broader Panel was front and centre of the event itself.  And
it was just great to see how popular the event was, many more
people coming to have a chat to us on the stand than would have
found us before, so, all in all, a really big highlight for
myself.  So, for you, Rich, are there any other highlights
that you want to call out for this year? 


Rich: And first to say, absolutely agree with the Research Summit
being, you know, a highlight.  The diversity of the
discussions that we had, it’s one of the things we enjoy most
about thinking about creating the summit, as you say, involving
the participants very much at the centre.  Like, physically
at the centre of the room, for people to come and talk to
participants and hearing stories.  And then really seeing
how over the years we can see the impact growing, and having
talks, whether it’s about individual findings, or big research
studies.  So the final talk of the day was from Charlie
Swanton.  He was talking about some really exciting work
that his team have done in our National Genomics Research
Library, making a really important discovery about extra
chromosomal DNA in cancer, and that’s now been published in
Nature.  And then right next to him, we were having a policy
talk from Sam, who’s the CEO of NICE.  And you can see the
range of things, the sorts of evidence, sorts of conversation, we
need to have, so that was really fantastic. 


I’d call out one discovery this year that maybe we’ll come back
to, and one other big highlight.  So I think the big
discovery this year was the discovery of this piece of non-coding
sequence in the genome called RNU4-2, which turns out to be
pretty much the most common cause of developmental disorders
that’s been discovered.  And it’s just so exciting to see
that having been discovered in the National Genomics Research
Library.  And then the news, the knowledge spread, across
the world, and family support groups coming together to
understand and learn more about what that means for them. 
So that was, I think, the discovery over the years at Genomics
England that’s touched me most, seeing that story. 


And I’d say for us, organisationally, another big highlight has
been the launch of our newborns programme, the Generation
Study.  So as lots of people listening will know, we’ve been
actually thinking about what the questions underlying this study
are for a good number of years, doing a lot of preparatory
work.  Actually, before we even started, setting up public
dialogue jointly with the National Screening Committee about what
the public were keen to understand and the appetite for research
in this area.  And then we’ve been spending several years
designing the study, working with the NHS how to design, safely
launch it, National Screening Committee involved all along, and
working with patients and the public to design it.  And this
year now launching the study at a public launch, just a couple of
months ago, by the time people are listening to this, and at the
time of recording, more than 2,000 families have joined the
programme.   


So really exciting, us exploring a really big question for
genomics, about the use of whole genome sequencing in newborn
babies.  Whether that should be offered to every baby at
birth, primarily driven by that desire to do better for those
children born with treatable conditions, where genetics,
genomics, can be a way in to finding them, but doing that at the
right pace, and very much in a research setting.  That’s
been a real, a moment, I think there’s been so much work on the
path to it, but it’s right to sort of celebrate these staging
posts on the way.  We’re early in the programme, there’s
lots to do, lots to work through, lots of evidence that we’ll
accrue, but it’s really exciting to be at that staging
post. 


Adam: No, absolutely, and from my side, I think seeing all of the
media pick up for the Generation Study launch, you could really
see the excitement in the wider kind of community.  Seeing
it shared on social media, obviously those part of the 100,000
Genomes Project, seeing things like this.  It’s like they
can see the tangible outcomes of all the work that they’ve done
as part of that initial project, and seeing how those learnings
are then taken onto this new study.  So we’ll now hear a
clip from earlier in the year from Louise Fish, who is the former
CEO of Genetic Alliance UK, who shares her thoughts on the
potential of the Generation Study. 


Louise: The Generation Study is looking at 200 conditions and
whether it’s possible to screen for them.  And for all of
those 200 conditions, it’s a really exciting opportunity to see
if we can learn more.  Both about the potential to
understand and develop treatments early, but also just about the
chance to understand the natural history of that condition so
much earlier than we do at the moment.  And I think that’s
it, it’s that understanding the natural history of the condition
really early, and understanding how a family can be helped,
through all aspects of the condition, which is giving people most
excitement I think, alongside the potential to develop
treatments. 


Adam: So now, let’s look back at the priorities for Genomics
England for 2025.  Now, Rich, would you like to just take us
through some of the things you’ll be focusing on next year? 


Rich: Yes, one of the things that we’ve been doing this year, but
also actually in the year before, is really looking to the
future.  And saying, where might we be in terms of genomics
really living up to the impact it could have, if we collectively,
in the UK and working with international partners, sort of get
things right?  And that’s very much about balancing the
realism of where we are, and the impact we’re already having, and
being proud of that, and then getting that same sort of ambition
and realism casting to the future.  And I’d say, I think
there are two really broad themes.  I think the first thing
is, we’re enormously proud of the impact we’ve had already for
families with rare conditions, and people with cancer, and that
impact will continue to grow in the coming years, in those
areas.  And in the next few years, that’s where the biggest
impact of genomics will continue, and the rare disease programme
we have thinking increasingly about how we support the generation
of evidence and pathways that lead to rare
therapies.   


So building, getting better all the time at finding diagnoses,
which is still a long journey we’re on, and continuing that
work.  Increasingly thinking about how we can support
therapies, and in cancer, again, playing a better role in cancer,
both by driving efficiency in diagnostics, and efficiency in
identifying where therapies enabled by genomics can be
targeted.  And we see lots of different examples of that,
clinical trials is a big area where we hope to have more impact
in the future, but also thinking about some of the novel
therapies that are there, both for rare conditions, but also, for
example, the cancer vaccines.  And I think we’re uniquely
placed in the UK, because of our partnership at Genomics England
with the NHS, and the broader science ecosystem, to have that
impact.  So that’s the sort of like continuing very much
where we are, but really pushing those boundaries. 


And then also, if we look to the future, to say, what role could
genomics play?  And we, as you know, our vision at Genomics
England is a world that everyone can benefit from genomic
healthcare, and I think that plays out in a couple of ways. 
Firstly, thinking about how we ensure the lessons we’ve learnt
through our diverse data programme is embedded across all of our
work, so that word “everyone” applies to people in lots of
different ways, different communities people come from, different
socioeconomic backgrounds, making sure that equity is based into
all of our work.  And then also, to say there’s real
opportunity for genomics to play a broader role than in rare
conditions and in cancer, we’re proud of the impact we’re already
having there, and we should really look to the future.  And
as we set out where we think what evidence is needed and where we
need to learn what the digital infrastructure that we build and
others build, need to build that to support that, we look across
a few different areas.  But really you can see genomics
playing a role across the lifetime, in different places in
different roles.  


To pick one really powerful example is something people often
refer to as pharmacogenomics.  Which is a medical term for
what boils down to look at a person’s DNA sequence, that’s the
genomics bit, and making decisions based on what drug to give
them, what drugs to avoid, or perhaps what dose to drug to give
them.  Based on, for example, the desire to avoid adverse
drug reactions that people might be at high risk of, and you can
identify that risk looking at the DNA.  That is one example
of genomics playing a role in being increasingly sort of
preventive, getting away from disease, getting upstream of
disease arising, or harm arising.  And there are other
opportunities in common disease as well, sort of casting forward
to what that impact might be, and we feel that genomics could
play a role, really broadly, across healthcare, in probably as
many as half of all healthcare encounters.   


But what we need to do over the coming years for that to
potentially be the case is we need to build out the evidence, and
we also need to understand what digital infrastructure we need,
to make that a possibility.  So that the information is
there in simple format, for patients and the public, for their
GPs, for their pharmacist, for people in any speciality in
hospital, not just sort of rare disease clinics or in cancer, as
we are at the moment.  And so very much we’re thinking about
the programmes that we and others could run to ask some of those
questions, to think about what we need to build out.  We
feel that the UK’s uniquely placed to develop that evidence, so
that we can make the choices about how genomics is used, and so
we can be ready to embed it.   


And it really aligns with that shift that we see and we hear, for
example, in government being talked about, when we’re looking
about sort of the shifts that the NHS sees as essential. 
You know, increasingly preventive, increasingly digital,
increasingly in the community, and that point of sort of getting
upstream.  And genomics is going to be an important part of
that.  And we at Genomics England are really excited about
the role that we can play, whether it’s through the digital
infrastructure we build, whether it’s the programmes that we run
to develop the evidence.  Or whether it’s through the ethics
and the engagement work, the work with the Panel, and the work
with the wider public, to understand how we might develop this
evidence, what people are comfortable with, what the expectations
are.  And I think that, pulling that together is complex,
it’s really exciting to think about how we do it.  I think
we in the UK are uniquely placed to take advantage of that. 


Adam: That’s great, and I think the pharmacogenomics piece is
fascinating.  I mean, you hear many stories of people having
adverse reactions to certain medications, and you wouldn’t even
think it’s something that may be linked to their genetic
makeup.  It’s so important that we take people along that
journey, around what the benefits are, the ethics, to make sure
that people really understand the journey that we’re making and
what the potential impact could be.  Whilst there’s lots of
amazing new areas to develop into, a key focus for us on the
Panel is really continuing to demonstrate how the 100,000 Genomes
Project participants continue to have an impact, and they’re
helping shape a lot of these developments.  So they
generously donated their data, it not only helps Genomics England
develop the systems and services that now benefit many families,
but it also continues to drive that scientific and technological
enhancement.  So it wasn’t just about reaching that 100,000
genomes, that project was really the starting point, as it were,
it’s not the finish line, it laid the groundwork for a lot of
these developments.  So it’s about how do we focus on
maximising the benefit for those participants over their
lifetime, not just at that one point in time.   


We know genomics is evolving so rapidly, what you can glean from
a genome today is far more than what was possible in 2013. 
And we know the Diagnostic Discovery team is continuing to
analyse the data for participants in the project based on these
new advances, the team led by Suzi (Walker), who’s doing some
amazing work there.  Using all the latest tools and
enhancements, just to make sure that those participants are
really benefiting from that learning.  So, we just need to
make sure we stay close to that wider community, and just ensure
they’re not forgotten, that’s really a key north star for us as
the Panel.  And something that we’ve been pushing is better
ways that we can help to communicate the ways that you're
celebrating these successes, providing regular updates on
research progress, offering personalised reports based on the
latest findings.  And it’s all about providing them with
that hope.  Some people may never get a diagnosis, but it’s
about giving the hope that one day they might get that phone call
out of the blue, so it’s about giving the hope that those
possibilities are out there for others.   


So we’re now going to shift gear onto hearing from Shaun Pye, who
is the father of Joey.  She was diagnosed with DYRK1A
syndrome, which is a rare chromosomal disorder, which causes a
degree of developmental delay or learning difficulty, at the age
of just thirteen.  In this podcast episode, Shaun and his
wife Sarah told us of their journey to Joey’s diagnosis, and how
their role in writing the BBC television comedy drama series,
There She Goes, has helped to shine a light on the rare condition
community. 


Shaun: Then the opportunity came along with 100,000 Genomes, and
we signed up immediately.  And then that, they did that, and
it was a few years before that went through the system, and then
we had, out of the blue really, we were asked to go and see a
geneticist, and we had no idea that this is what it was.  I
honestly thought it was just a routine sort of, we’ve got a few
more theories or something, and she just said, “We’ve found out
what it is.”  And it’s like, that moment is, well, we tried
to describe it in the TV programme, but it is quite hard to
describe what goes through your mind, when after thirteen and a
half years somebody suddenly says, “Oh, by the way, that thing
that happened with your daughter, we’ve worked out what it
is.” 


Adam: So here, Rich, did you want to provide some updates around
future progress, particularly in diagnostic discovery and
expanding the research? 


Rich: When we’re looking to the future, we’re looking sort of in
two areas.  How we can build the impact we’re having today
for families with rare conditions and cancer, and that very much
includes the participants in our programmes, 100,000 Genomes,
those through the NHS Genomic Medicine Service, who joined the
National Genomic Research Library.  And we’ve seen, I think
the number that I’m most proud of at Genomics England is that
number of diagnostic discoveries returned to the NHS, which has
just hit the 4,000 mark.  And for those less familiar with
the terminology, essentially what that means is where either
researchers or the internal team at Genomics England have
identified changes in the genome data, that with new knowledge,
often with a fine tooth comb, it’s considered likely that that is
the answer to the cause of the rare condition in that person in
the programme.  So that’s 4,000 of those returned to the
NHS.   


And that tells you a lot about where we are for families with
rare conditions, and I think there’s two points here.  The
first one is, we’ve got a long way still to go to do what we want
to for families with rare conditions.  I’m a doctor and
still see families in my clinic once a month at Great Ormond
Street, even with the incredible advances we’ve had over the last
particularly 10or 15 years, with the changes in sequencing and
analysis, we still find an answer for the minority of
families.  So that number is growing, and we’re really proud
of how much better we’ve done, and there’s a long way left to
go.  And the really critical thing is designing a system
which we’re so lucky with in the UK here, where we can continue
to learn.  And that’s not just for learning for the
knowledge of people who might encounter the health system in the
future.  It’s to learn for those people who’ve joined the
National Genomics Research Library, who’ve already trusted us to
be the custodians of their data, and to do better in the
future.  And that’s what our diagnostic discovery work
really aims to do. 


And sometimes that’s about new gene discoveries.  So all the
time new things are being discovered each year.  And if you
look at the DNA code, if you like, boil it down very
simply.  99% of it is what we call non-coding DNA, I’ll come
back to that, about 1% is the genes, which if you like are sort
of the books in the library of the DNA, overall DNA code, that we
understand relatively well how they’re read by the body. 
The bits in between, it’s a bit of a funny, well-spaced out
library this one, that’s the 99%, actually we’ve had very little
understanding of most of that code in between.  But we’re
beginning, and particularly this year, to gain an understanding
of how we might interrogate some of those pieces.  And not
all of the answers lie in that non-coding DNA, there’s lots of
answers still left in genes that we don’t understand
well.   


But one of the examples I mentioned earlier, and in fact the
thing, the single discovery I guess which I’m most proud of
having happened in the National Genomic Research Library is this
discovery of this non-coding region called RNU4-2.  Which is
a funny, like technical series of letters and numbers, but
basically it’s a very small patch of the whole DNA code. 
Where this year, scientists discovered actually about 60 patients
in the families in the National Genomic Research Library where
that was the cause of their child’s developmental disorder. 
Actually, that knowledge has really rapidly spread across the
world.  So I actually saw on social media at the weekend,
from one of the scientists involved in the discovery, that the
family support group that’s been set up for what they’re calling
ReNu syndrome, which I think is a lovely name in itself, speaks
to that word hope that you mentioned, Adam.  There are now
248 members of that group, and that’s how fast that knowledge
spreads across the world. 


And what we’re doing is thinking how we can support those
discoveries more broadly, and non-coding DNA is one of those
areas where that growth is, but it’s not the only one where we’re
looking to support things.  But it’s so exciting, and I
think it gives you a sense of the scale of progress that is left
to make.  And I think a really important point is that
remains a really important area of our focus, it’s not about
moving on and looking just to the future, but we need to keep
working for the families who are already part of our
programmes. 


 


Adam: That’s incredible, that 248 members in such a short space
of time.  And I love the ReNu name for that, I agree, I
think that’s a fantastic way of positioning it.  Earlier
this year, we heard from Lindsay Pearse, whose son Lars received
a diagnosis through that groundbreaking discovery of the genetic
change in the RNU4-2, or ReNu gene, which was made possible by
whole genome sequencing.  She told us what the diagnosis
meant for their family. 


Lindsay: This feeling that, like, we’ve been on this deserted
island for eight years, and now all of a sudden, you're sort of
like looking around through the branches of the trees, and it’s
like, wait a minute, there are other people on this island. 
And in this case, actually there’s a lot more people on this
island.  Yes, it’s very exciting, it’s validating, it gives
us a lot of hope and, you know, it has been quite emotional too
(laughter).  And also, a bit of an identity shift, because I
spoke earlier about how being undiagnosed had become quite a big
part of our identity, and so now that’s kind of shifting a little
bit, that we have this new diagnosis, and are part of a new
community. 


Adam: You talked about it there, Rich, I mean, it’s been really
seen as a success story for the whole genomics ecosystem,
especially the speed at which it all came together.  From
the conversations I had with some of the individuals that were
involved in the study, from the date of seeing the first findings
in the lab meeting to a polished pre-print going live, was
exactly 47 days, which in science terms is less than a
second.  So that’s how they positioned it to me,
incredible.  And you’ve just said there, they set up this
support group earlier this year, and already got 248 members,
which is incredible.  The impact on families is significant,
the mother touched upon it there.  I mean, for many parents
there is that relief that it wasn’t something they did during
pregnancy, but instead, it is a chance occurrence.  For
some, this knowledge means that they can make important
decisions, choosing to grow their family, for example.  And
it really ends that diagnostic odyssey that many families face,
providing answers and potentially ending unnecessary testing that
their child is going through. 


But I think, and I can talk from personal experience here, that
the largest impact is really being able to connect with other
families and building that community, you cannot really
understate that.  If I look at our own experience of getting
a CRELD1 diagnosis for our children, the first time we didn’t
feel alone was when we could find that community.  We can
support each other, we can learn from each other’s experiences,
and really also drive forward further research into that
condition through advocacy.  So, I remember seeing that post
on the Facebook page, about that RNU4-2 discovery, and this was
before I’d even started in the role at Genomics England on the
Panel, but you could really feel that excitement and the relief
that they had.  And they mentioned that the official paper
only had 36 other people worldwide, they found this little
Facebook group that they created with five families in, and in
the space of, what, 6, 7 months, they’re already at 248. 
That’s all people that understand what they’re going
through. 


And it’s really hard to describe, it’s like finding your family
that you’ve never met, people that understand, and they really
get what you're going through.  And being able to share
tips, advice, learnings, and things that everyone’s going through
at different stages in their child’s life.  So, I really
don’t think you can talk highly enough of that, that community
aspect, and that’s just been amazing to see.  And, look,
this new era of research into the role of non-coding RNA genes,
it really may open more opportunities for diagnoses for patients,
participants potentially leading to hopefully more breakthroughs
in the year ahead. 


So now we’re going to move on to why it’s so important to engage
patients and participants in the genomics world.  So, we’ll
now hear a clip from Helen White, who is the Vice-Chair for
cancer on the Participant Panel.  Now Helen and I have been
working really closely together as Vice-Chairs in this interim
leadership role, to really ensure that we continue advancing the
Panel’s strategic initiatives while we recruit that new
Chair.  So it’s been amazing learning and working with
Helen.  In this clip, she discussed an important topic
that’s been very much top of mind of the Panel, which is the
importance of involving the patients and public in genomics
research. 


Helen: I think, you know, as patients, members of the public,
we’re eager to get on and for change to happen and things to be
better, but it’s, yes, a big, big process.  But also, good
to hear that you talk about it being a collaborative approach,
it’s not just Genomics England, it’s the NHS, it’s members of the
public and patient voices, it’s other organisations working in
partnership. 


Adam: Now I think we all recognise the importance of engaging
patients and public to ensure diverse communities understand the
benefits of genomics, and actively involving patients and
participants in the research, to make sure that they’re including
the perspective of what matters most to them.  


Rich: I mean, it goes back to the thing that we really see as
central to the value that we at Genomics England can
provide.  So we increasingly think of ourselves as a data
and evidence engine for national scale genomics, and I think a
really important to call out there is that evidence is
broad.  And part of that evidence is about public
expectations, public preferences, and patient preferences. 
And if you think about the big things that we do and where we
bring that value, and bring that data and evidence engine role,
is, you know, firstly in the digital infrastructure that we build
and the data that we hold and present to our various users. 
Secondly, it’s in the evidence that we distil from that, and very
much thinking about part of that being evidence in and around,
including that piece on what people expect, this isn't just about
hard science and health economics, this is an equally if not more
important part of that.  And then thirdly, it is the third
area of our focus is on that engagement piece, because that’s so
fundamental. 


And I think you and Helen called that out absolutely right, about
that being, that’s integral to the whole process, and it’s the
beginning of any programme you need to start with understanding
what the big drivers are, what the expectations are, and doing
this very much together.  That’s one of the reasons we’re so
fortunate to have the Participant Panel we do, in our Newborns
Programme the Panel have been an important part of that design
from the outset.  It’s also about broader engagement with
different communities, people who currently don’t engage with
genomics, because they’ve had no need to, sort of understanding
that piece.  And I think we’ve definitely seen over time in
health data research, but also research more broadly, where it’s
quite easy for these things to be disconnected.  And that
results in two things.  It results in research happening
about interesting esoteric stuff, but not on the stuff that makes
a difference for families.  And I think that’s really
important, because researchers need to be directed in the
resource limited world towards the things that really make a
difference.  So that’s the first thing. 


And the second thing is, it’s very easy, with the best will in
the world, for people to make wrong judgements about what people
are or aren’t content with, and you need therefore to be
absolutely transparent about what the research is.  Be
really clear about what those questions are, and let people
challenge you, right from the outset, so that we can design
research studies, but also, the system as a whole, together
in a way that everyone has a say.  Not everyone has the same
view, but how we can develop a system that takes into account
those things and gets that balance right.  This is about
making a difference to people’s health outcomes, thinking about
how we achieve that, while also balancing off all of the
different views there are, is really important.  And that’s
at the heart of it.  And it can be scary, because it’s right
that there is that challenge out there.  And it’s one of the
things that I think we’ve learnt at Genomics England, how
important it is to be really open to that challenge, and to do
that piece really early in all of our work, and have it there
baked into our governance as well, for example, the Participant
Panel. 


Adam: Absolutely, and I think you’ve summarised all the key areas
there really well, in terms of the importance of that
engagement.  And one other area I’d just like to pick up on
is the impact it can have on the patients or the participants,
simply by having that connection with the researcher, that’s
doing all of the amazing stuff that for some of us, it’s really
hard to comprehend.  But having that interaction and
collaboration with them, it’s so important in terms of, again, I
go back to giving you that hope.  And a real highlight for
me at the Genomics England Research Summit was when Hannah, one
of the members of our Panel, she came running over to us and she
was just beaming.  And she said, “Guys, you’ll never guess
what, I’ve just met the scientist who discovered my daughter’s
diagnosis in the NGRL.”  And you could see that she was so
excited, you cannot understate the impacts that can have on them
as a family.  Like having that interaction and that personal
connection with the person that really in some ways kind of
changed their lives, in terms of understanding more about what
that could mean for their daughter growing up, and how they’re
managing the condition.  So, it’s amazing when you can see
those highlights and hopefully we’ll see more of those. 


And it’s also really important that we get that diversity I
think, as well, in that collaborative approach, just to make sure
that it is equitable for all.  And that really brings us on
nicely to the next topic, which is about how do we bridge the gap
between those diverse communities, and make sure that we’re
reaching everyone as best as possible?  So we’re now going
to hear a clip from Sandra Igwe.  Sandra is a CEO and
founder of the Motherhood Group, speaking about the Generation
Study.  Now, Sandra spoke about the importance of building
trust, and how it is vital to engage with a diverse group of
communities in the design of research studies. 


Sandra: Every community’s different, and every patient is
different as well.  And so that may require different
focuses or different formats or different messengers for
different groups.  And so we like to have people with lived
experience from the community representing that, and also driving
the uptake of consent as well.  But failing to engage
diverse voices can lead to perpetuating inequalities in access
and uptake.  So it’s really important to have
representation, because the lack of it in research can overlook
communities’ specific concerns and needs. 


Adam: So, Rich, did you want to talk about why it’s so important
to have that diversity? 


Rich: Yes, I mean, it’s critical.  One, I mentioned earlier,
our vision as an organisation is a world where everyone benefits
from genomic healthcare, and that word “everyone” really
resonates.  I think Sandra has been really an important part
of the work that we’ve done over the last couple of years,
particularly through our Diverse Data programme.  But I
think one of the real challenges for us is how we make sure that
that is something which is embedded across all of our work. 
And that’s something that we’re really focused on at the moment,
how we embed the learnings that we’ve had through that standalone
Diverse Data programme into everything we do.  Because we’re
absolutely committed to that, and I think that is engagement with
the diversity of different groups relevant to each
programme.  I think one of the real important things is that
transparency piece about actually that it’s hard to achieve
equity in healthcare, full stop, because of historical
underinvestment in some of these areas.  And I think being
clear with people about that is a really important step, and then
talking really practically about why it really makes sense to
take different approaches. 


And so one thing about our programmes and how we think about the
future overall, if genomics is going to make a difference to more
than half of healthcare encounters, it needs to be something that
across all communities, and across the large majority of people
in each of those, that this is something that they want to be
part of.  Because it’s going to make a difference for them
or their families or something they really buy into.  And
that’s why this isn't just about thinking only about specific
programmes where this is a question, it’s about making sure that
we’re designing a system, developing the evidence that is really
broadly applicable, and continues to learn.  Because we know
that what we learn today is hopefully an improvement on where we
are, but we continue to learn and learn and learn.  And it’s
about creating a system that does that, and does that equitably,
or as equitably as we can. 


Adam: So we’re now going to hear from Moestak Hussein, who works
to build and embed cohesion, inclusion, and social justice, in
her role at Bristol City Council, in public health and
communities.  Moestak talks about the value of
co-production, and how this can help to build trust with
communities who have historically been underserved or
mistreated. 


Moestak: If we talk about co-production, true co-production is
really creating a power balance where there’s no hierarchy, it’s
an empowering model.  It empowers both the researchers or
the person that comes in, but also the communities that
participate, and you all start on the same level, on the same
outcomes and the same goals and aims that you want to
achieve. 


Adam: So, if I look at that from our perspective on the Panel, I
think co-production in genomics research, so using participant
data in the NGRL, is certainly what we’d like to see much more
of.  To ensure that research is not only relevant to its
intended audience, but also aligns with broader democratic
principles of citizenship, accountability, and that transparency
as well.  But look, we have to be realistic.  Some
genomics research projects are not going to lend themselves to
meaningful patient and public involvement in the early stages,
but it’s really important later on in the research pathway, if
the findings identify a patient population who might benefit from
that research.  At the moment, involvement of patients and
participants, carers in research, is really not great, in terms
of the researchers using the NGRL.  So, in conversations
what we’re hearing is they’re saying, “Well, we don’t know how to
do it, we don’t know what steps we should take.”  Or “We
don’t think it’s relevant because we do this particular
research.”   


But really, our view is that some PPIE, or patient and public
involvement engagement is better than none.  Some may not be
relevant for all stages of the research pathway, we’re not really
seeing enough of that happening at the moment, and some papers
are even being published without any context of the participants’
lived experience at all.  Which can actually be quite
frustrating, if you're that patient or parent, and you see a
paper published, and you think, well, actually, why didn’t they
reach out to us?  Just to understand a bit about the
symptoms that we’re experiencing, what are the challenges that
we’re facing, just to really add that important context. 
So, I think there’s certainly an opportunity for us on the Panel,
certainly for Genomics England, to be that kind of guiding light
for those researchers.  Whether it’s providing them with
researchers, research papers, or a hub of patient advocacy
organisations that are already connecting those patients with
researchers.  It’s all about signposting them the relevant
information, so I think there’s certainly things we can do
there. 


And it really fits in with the bigger engagement piece.  So,
whether there’s a landing page or a dedicated website that shows
them, where do they go, what are the steps that they can take,
what’s the best practice, what’s worked well for another
researcher, and how did that lead to really great outcomes for
the families involved?  That’s where I think we can all play
a part in guiding them on that journey, rather than it just being
a case of, they’re not doing that patient and participant
engagement very well, and kind of criticising it.  Let’s
reach out to them and say, “Look, we can help you and guide you
on that journey.” 


Rich: I really agree with the need to make those connections
happen.  One of the things I think that is often missing is
just a confidence just to crack on and do some of this
stuff.  And I think, actually, looking at the ReNu syndrome
experience, that was work that was swiftly done.  Scientific
at the beginning, the initial publication put out there so that
people could understand, and was quite medical by necessity, in
terms of the speed of getting information out there.  And
then very quickly, and quite organically, patient support groups
have formed, and also, the scientists are working with that
group.  I had a really interesting conversation with Sarah
Wynn, who’s the CEO of the Unique last week, about how some of
that has played out, how the role they’ve played in facilitating
some of that.  And some of it just comes down to sort of
really simple things, and working through how you can set up Zoom
or whatever meeting, for people to learn about the
condition.  And how you preserve anonymity, where that’s
appropriate, but also allow people to have discussions about
their loved ones where they want to, etc. 


So it’s partly just about giving people the space and the
confidence to get on with some of these things.  And as you
say our, one of the things we at Genomics England are quite
thoughtful about, and I think it’s a really good topic to
continue talking to the Panel about, is how we get that balance
right.  Where, actually, us being a connector and, as you
say, signposting useful resources or ways of doing these things,
just to break down some of those barriers.  Because almost
always the research groups, when they discover something new,
this is really new territory for them, and they’re often nervous
about doing the wrong thing.  And so it’s about breaking
down some of that anxiety actually I think. 


Adam: Yes, absolutely.  In our case, with our condition that
we’re advocating for our son, we’ve been working with a
researcher.  And it’s almost on us as well just to kind of
share our story with them, and making them feel more comfortable
to ask us questions and be very open and transparent about the
more we can share, the more that can hopefully benefit their
research moving forward.  It’s very much a two-way thing as
well, but I like what you said there about having the confidence
just to kind of reach out and start those conversations, and have
that starting point. 


Next topic, we’re going to look at some of the innovations that
are on the horizon, that we’re seeing in the world of
genomics.  So, Rich, do you want to take us through what are
the most exciting things that you're exploring at the
moment?  I know we hear a lot about AI and the technological
aspect, so why don’t you take us through some of those? 


Rich: Yes, so I guess this comes back to that question where
we’ve been looking forward, you know, where might genomics be
impactful and making a real difference to people’s lives, to
helping us have a more efficient healthcare system in the
future?  And I think part of that is about this general
shift.  You know, genomics technology, we just take for
granted now how much it’s shifted, how it’s within the means of
the healthcare system to generate genomic data.  And we’re
really fortunate in this country because of the digital
infrastructure that we’ve been able to build together with the
NHS, that opens up a lot of these questions.  And it’s just
extraordinary the time we’re at in genomics, so almost take those
two things for granted, which we should never do.  The
change in genomic testing technology, which continues to advance,
and secondly, thinking about the digital infrastructure, like the
nuts and bolts of what we’ve got, and the ability to safely store
and reuse and analyse some of that data at scale. 


And point at two big things.  Firstly, genomics enabled
therapies are changing a lot.  So, our understanding, our
ability to make a diagnosis, or understand what’s different about
a cancer, for example, mean that in various ways it’s becoming
feasible to do more tailored therapies.  Where knowing that,
the genomics nitty-gritty of that condition, helps you tailor
that, or create sometimes even a bespoke personalised, truly for
that one individual, therapy.  And in rare conditions we see
that with the so-called N=1 therapies, but also with gene
therapies and so forth.  And in cancer we see that with the
cancer vaccines, for example.  So that’s an enormous area of
change, and one of our responsibilities is to support that sort
of research, to help identify people who might be eligible for
trials or treatments.  But it’s also to work with the
ecosystem to think about how we can help support the generation
of evidence that means that those therapies can be affordable and
so forth, on a scalable basis.  So that’s one really big
area of excitement.  And we see our Rare Therapies Launch
Pad being part of that, the National Cancer Vaccine Launch Pad,
being part of that.  So that’s thing one. 


Thing two is AI and machine learning, and I think sat on
alongside the sort of broader picture of saying, there’s a lot
left to learn, there’s enormous potential in genomics in terms of
playing a role in many different situations, not just in rare
conditions, in cancer.  And we know doing that well, but
also scaling it, making it really efficient, so that we can do
that in a context of a really busy health service, one of the
answers is making sure that we’re leveraging everything we can
about the potential of AI.  And there’s lots of different
ways in which that can be supportive, I won't list lots of
them.  But one of the things that we’re doing at Genomics
England and working with the NHS is thinking about the most
promising areas.  And some of those are quite, like, down
and dirty, if you like, so sort of saying, which jobs are there
that we can use AI, if you like, as a co-pilot, alongside
experienced scientists, to speed up their work? 


And we’re really excited about the role we can play in a few ways
actually.  So the first one, back to that sort of data and
evidence engine point, is helping organisations who have a tool,
help validate it for use in the NHS, and say, “Does it perform to
this standard?  What do we want to say about how it performs
from an equity point of view?  And from a clinical safety
point of view?” etc.  And making that leap from stuff that
makes a Nature paper to stuff that lands in clinic is
surprisingly challenging, and that’s one of our roles.  And
we really enjoyed working with various companies and academics
over the last few years on that.  We did some work recently
with Google DeepMind, on their AlphaMissense tool, thinking about
how we can think about that role that might play, for example, in
speeding up the interpretation of rare variants that might cause
rare conditions.  And there’s enormous potential in all
sorts of different parts of the sort of end to end of genomics
playing a role in healthcare. 


And then I’d also say one of the really important things is
because genomics in many ways just needs to be part of healthcare
and not be treated differently, we also need to recognise where
there are questions we need to work through really thoroughly
that are a bit more bespoke.  And one of the things that
we’re really committed to doing, as we look to the future, is
making sure that we can support on some of those questions that
we really need to be clear on.  I’ll go back to that point
on, what do we mean about making sure we understand how a tool is
working, and whether it’s producing results in an equitable way
for all different communities?  How do we understand
that?  How do we explain what we understand about the
performance of a tool?  How do we make sure that patient
identifiable data remains non-identifiable if a tool’s been
built, trained on data?  Working through some of those
questions. 


But they’re really important for us to do, and we’re enormously
excited about the potential, and we’re really committed to
working through in detail how we can make that path to adoption
safely and in the way that everyone would expect and desire as
rapid as possible.  We’re just one step in that
process.  But we really see a sort of important role for
helping people who are producing various tools or various use
cases, helping them prove them, helping them validate them, and
making the system more efficient overall, but in ways that we
really understand. 


Adam: That’s fantastic.  Look, not that I'm biased at all,
but I can tell you that the AlphaMissense innovations that are
being developed are shared a lot internally at Google, it has
been seen as an amazing success case.  So hopefully we’ll
see more on that moving forward.  But in the next clip,
we’re going to hear from Francisco.  So Francisco is the
Director of Bioinformatics at Genomics England, who tells us more
about the application of AI and its benefits in genomics in
healthcare. 


Francisco: So AI is already driving the development of
personalised medicine for both research and healthcare
purposes.  Now at Genomics England we are investigating the
use of AI to support a number of tasks, for the potential impact
in both research and healthcare.  In the context of
healthcare, we are talking about AI tools that can support the
prioritisation, the ranking of genomic variants to allow
clinicians to make more accurate and faster diagnosis. 


Adam: While all of these innovations sound really exciting, it’s
really important that we just continue to bring that patient and
participant community on that journey, just to ensure that they
really understand the full benefits, and we talked about that on
the episode today.  I know that the panel has always
encouraged Genomics England team to look at its boots while
shooting for the moon.  I really like that phrase, just to
make sure, look, we can’t forget where we’ve come from to make
sure we’re taking people on that journey. 


So, we’re going to wrap up there.  Thank you to Rich Scott
for joining me today, as we reflected on key milestones for 2024,
and looked at the year ahead for both Genomics England and the
wider genomic ecosystem.  If you enjoyed today’s episode,
we’d love your support.  Please like, share and rate us on
wherever you listen to your podcasts.  I’ve been your host,
Adam Clatworthy, this podcast was edited by Bill Griffin at
Ventoux Digital and produced by Naimah Callachand.  Thank
you everyone for listening.