How Genomics Supports the Patient Journey

Hello, and welcome to The Road to Genome podcast series.

I'm your host, Helen Bethel, genetic counselor and workforce development and education lead for the North Eastern Yorkshire Genomic Medicine Service.

Today, I'm at Sheffield's Northern General Hospital in the Clinical Genetics Department, as I'm joined by Dr.

Jackie Cook, consultant geneticist and rare disease clinical director for the North Eastern Yorkshire Genomic Medicine Service.

Hi, Jackie, thanks so much for joining us today.

So I was going to start by asking you, what is your current role and how many hats or titles do you currently have at the minute?

So my day job is a consultant clinical geneticist at the Sheffield Clinical Genetics Service, predominantly doing cancer genetics, but also quite a lot of adult genetics and hats, lots of hats.

So I am the clinical director for rare disease for the North Eastern Yorkshire Genomic Medicine Service.

So basically that means I am responsible for delivering a genomic service across the region, but based on rare disease.

There's another clinical director who is responsible for cancer.

I am also within the laboratory service, the rare disease lead in the genomic laboratory hub for North Eastern Yorkshire as well.

But the two roles really overlap and I think it's probably become one job now.

Fantastic.

And is this the job that you always aspired to do?

At heart, I am and always will be a doctor.

That's what I do.

And that's what I have aspired to be since kind of I started medical school.

I think one of the things that happens as you become a senior consultant is that you can go a number of ways.

And one of those ways is to take on an increasing management role, which I have done.

And I have enjoyed it and find it challenging.

Not sure I ever aspired to it, but it's something that happened over the years.

When you were younger than Jackie, what was it you thought you would do when you were grown up?

I had no idea what I was going to do when I grew up.

I had no idea until I had to start thinking about university.

And that was the first time that I started looking at careers.

I was doing maths, physics and chemistry at A level.

And so it was clear that I was kind of heading in a science direction rather than an arts direction.

And then I just thought, well, what about medicine?

And the more I looked into it, the more I thought, actually, that's what I want to do.

So it was only at that stage, really about a year before I started university that I made that decision to go into medicine.

And what was it that particularly drew you to medicine at that time?

I think it was the fact that it is such a broad discipline.

So there's so much that you can do within it.

I think it is the fact that it is working with people, with patients, but using your brain to do it.

So it's the intellectual part as well that attracted me.

Yeah.

I think I hear you because I feel like it's the combination of bringing science to people and bringing it both together.

And I think it's the unique element of that.

And do you remember when you first heard the term genomics or genetics in amongst?

So I trained at Oxford and that's quite an academic medical school.

And so genomics was, well, genetics anyway, was certainly very much on the pre-clinical curriculum.

And so for probably training in those days, it was quite rare to do genetics, but actually because of where I was training, we did do quite a lot of genetics.

And did it inspire you when you first did it or did that take a while to come?

Oh, it inspired me.

So it was one of, I think, the most interesting parts of the kind of scientific part of my training.

And did you know from that instance then that that was the route you were going to take?

Well, no, not at all, because we're talking about the early 80s here.

So this was the right at the very beginning of genetic knowledge with regard to medicine.

And at that time, there were no clinical genetic services.

So it wasn't a career.

You could think, oh, I'm going to go into clinical genetics because it didn't exist.

So no, it's just something that I knew I was interested in.

So at which point in your career then did it start?

Because obviously we now have a genomic medicine service.

So at which point did that start to change?

So the first clinical genetic services were set up in the late 80s and early 90s.

So that's when it started to change.

When I qualified, I started training in adult medicine and rotating through a number of specialties, but finally ending up in renal medicine.

So I was a renal registrar up in Leeds and got to the point where I had to decide what specialty I was going to train in as a consultant.

Was I going to stay in renal or was I going to move elsewhere?

And they had just advertised the very first senior registrar post in the Leeds genetics department.

So I went along and spoke to the consultant there.

There were two of them in the whole department.

And said, look, I'm really interested in genetics.

Can you tell me a bit about what this job might involve and what the career might be?

And I sat in on a few clinics and then he went, just apply for it.

So I applied for it and I got it.

And it's interesting because my renal consultant at the time was just so cross with me.

He said, he wants to know why I was applying for a Mickey Mouse specialty.

Because it was that new.

Because nobody did clinical genetics.

What on earth did I think I was doing?

Throwing my career away, doing this kind of weird and wonderful thing that wasn't going anywhere.

Yeah.

Except that it did go somewhere.

And things moved on obviously and have done in clinical genetics quite rapidly.

So how many years have you been in clinical genetics now?

tarted as senior registrar in: 1992

So that's 31 years.

Wow, that's fantastic achievement.

What's changed in those?

Everything.

If there's no resemblance at all now to what it was when I started.

So when I started in: 1992

We could do one gene test.

That was the common mutation in cystic fibrosis and the Huntington's gene had just been discovered.

So we were doing predictive testing using linkage because we didn't know what the gene was or what the change in the gene was.

So the molecular side of genetics really barely existed in those days.

The career was all about pattern recognition, identifying syndromes, looking at predominantly children, lesser extent adults, and just recognizing what they had because they fitted the textbook.

You'd seen it before, so you knew what you were looking at.

Yeah.

And with the adults, some of the more classical syndromes, because of their symptoms, we could diagnose and advise about inheritance patterns and recurrence risks, but we couldn't confirm anything.

It was just, I think I know what this is.

But what a fantastically exciting time to be in this new growing area of medicine and being part of that right from the outset.

Yeah.

So from then on, the genes came through rapidly and the way we tested for them changed radically.

And so each year would bring on a new group of conditions that we were now in a position to diagnose, new tests that meant we could look at things in far more detail.

You know, there are some huge changes in technology that made a huge leap in what we could do.

And yeah, been there through it all.

Fantastic.

Fantastic.

So which bits of your job do you most love today?

So I think as a consultant, I don't get to see the easy stuff anymore.

I get to see the really hard and complex stuff.

And it is taking one of those cases and just thinking, what is this?

What could this be?

What tests do I need to do to prove whether I'm right or whether I'm wrong?

And then how am I going to explain that really complicated result to a patient in ways in which they can understand and it is meaningful for them?

And of course, we see all different types of patients, from people who have PhDs in genetics to people who've got learning difficulties.

And so each patient is different and you would have to pitch it in a different way.

That's the challenge that I really enjoy.

So on the reverse side of that, which are the most challenging bits of the job, would you say?

I think the most challenging bits are when you come up with something that is right in that grey area and there's a lot of grey areas in genetics.

So you just cannot say that it is that or that it isn't that.

And that, I think, is the most difficult thing for patients to get their head around.

They assume that we are either going to say it's that or it's not that.

And when we go, well, we just don't know.

I think patients find that really, really difficult.

And some cope with that uncertainty better than others.

And some cope really badly.

And those are the challenges which I think we all face and which can be very difficult.

Yeah.

Yeah.

Thinking about a kind of typical appointment then, what's that like for you?

So for me, the referrals come in and we then work out as a department who's going to see what.

So if there's something that clearly I have to see, I start off by trying to get as much information as that patient as I can.

So it's important to know what's happened to them in the past.

What investigations have they already had?

So I can start to put together a kind of picture in my own mind of what we need to be thinking about, what are the possibilities here, what is the differential.

Then often, because I am nowadays seeing the incredibly rare, I will need to do some reading around it because I don't hold all of that in my head.

So I will need to do some research myself and just find out what is the latest understanding of that, so that I can then work out what I need to be looking for when I see the patient, what I need to be asking them, what further information I need and then what I need to be arranging in terms of testing.

So all of that happens before there's a lot of work before you see some of these more complex genetic patients.

And then I see them and then you might have to do a complete u-turn because you might think, oh wow, yeah, I've got that wrong.

It's something else.

I need to be thinking something else.

So you need to be on your feet a bit and then following the appointment, obviously, I'll start arranging what needs to be done.

And then we always write patient letters getting that on paper, an explanation of what we're doing, why we're doing, how it's going to go from there.

Yeah.

So that's most of it.

Yeah.

Fantastic.

And you mentioned about doing reading around the patient and as you say, not holding it all in your head.

What types of resources do you tend to go to?

We use PubMed a lot.

So we're looking at recent medical publications.

So we use PubMed.

There are various databases that we use and we use them a lot when it actually comes to results back and looking at what's been found and what's known about those particular mutations.

So yeah, mainly PubMed and then the genomic databases.

Can you tell us a little bit about what you do when you get a result back?

So how do you work out what that result means for the patient?

So obviously with a genomic result, there's a lot of information already on the report that you get back.

As a clinical geneticist, you can't just read the first line.

You've got to read it from top to bottom, because most of the interesting information is at the bottom of the report that nobody else reads, but you've got to understand it.

So you need to look at that gene fault and think, how likely is it that this is the cause?

Are we looking at something that's really certain, or are we looking at something that maybe, but there's some uncertainty there?

And it's that point when there's some uncertainty that you might want to either talk to the lab and get their view in a bit more detail on it, or go on to the database at that stage and just see yourself what's being written about that particular change.

And I guess that goes back to what you were saying earlier about the interest that you had in the science of it in working with people that in genomics, there is still a lot of that science that is not black and white.

And so there's still a lot changing.

There's a lot, you know, results aren't necessarily, as you say, always black and white, that there's often a lot of reading and analysis and science that goes into it.

Yeah, and that is the role of a clinical geneticist.

So we obviously, we use the word mainstreaming to describe genetic testing ordered by more mainstream specialists.

And we're not expecting to do all of that.

And I think that's a message we need to get across sometimes because one of the things that puts people off ordering genetic tests is I'm not going to understand it when it comes back.

A lot of genetic tests are very straightforward and simple, and that's fine.

The role of clinical geneticists nowadays is to deal with complex stuff.

And then you're often into pure science.

And so that is still an important part of the job.

Yeah.

And so do you have a particular preference for what type of cases you find most challenging or rewarding?

Do you still have a preference for a disease, or do you still like your renal work that you did?

So I try and combine it.

A while ago now, as genetics was expanding quite rapidly, it became clear that clinical geneticists either had to decide to be a jack of all trades and a master of none, or to sub-specialise and say, actually, I'm going to stop doing this branch of genetics.

I'm going to concentrate on this.

And given that I had an adult background prior to coming into genetics, it was obvious that I was going to do the adult side rather than the paediatric side.

And so I am the only cancer geneticist in the department.

So I do all the cancer genetics.

And I do a proportion of the adult genetics.

And of course, the renal is in there as well.

So I have run a joint renal genetics clinic with the renal team here for the last 15 years.

And do you find that rewarding?

Yeah, I still get a bit of a kick out of doing a bit of renal medicine.

It was nice at the beginning to just go back to it.

And it changed a lot, obviously, with all the genetics that's in there.

But yes, I still find that really interesting.

And I guess it must be nice going back to your roots, kind of seeing that update that genomics has brought and seeing where you left it and almost revisiting it at a later date to see where some of the answers came.

Yes.

And we've still got families where we've finally got an answer after years and years of looking.

But one of the things when we set up the clinic 15 years ago, the first thing that we did was join up all the families.

The renal clinic had all these individuals.

They had no idea they were all related to each other.

And we were just putting families together at the start going, well, their cousins, you know, they're all related.

It's all the same thing.

You only need to find one thing and we've answered the whole family.

But that had never been done before.

People, because they had different surnames, nobody realized that they were all related to each other.

And I guess that's where clinical genetics comes in, in being that kind of pulling families together.

So for patients where you don't have an immediate answer for them, how do you keep in touch with them and get in touch with them at a later point in time?

So there are some patients that you see that you know it's probably not genetic.

There's no point in pursuing this.

You've probably done what's appropriate to do and they can be discharged.

You've kind of answered a question, how likely is this to be genetic?

And the answer is not likely.

And then there are other patients that you see you know, you just know that this is genetic.

It's just you can't find the answer.

So the way we look after those patients, we do put them on review.

But often what happens is that something is published, something comes out and you think, that's what it is?

That's what it is.

Then you have to remember who it was that you got.

So that can be difficult at times, but you can just go back and think, I know what that is.

I know how to test for this now.

And you pick them up at that point.

How do you find patients react when you have an answer for them?

I think they're just amazed that you thought of them.

I think, you know, it's usually faced with surprise that you've actually recontacted them.

And usually that is met with, you know, they're pleased that you've done that.

They're grateful that you have done that.

So it is very rare for anybody to turn around and say, you shouldn't have done that.

People generally want an answer.

Sometimes a new gene has been discovered and we have gone back and retested.

That I think universally was appreciated.

Nobody said to us, you shouldn't have done that.

And you mentioned about knowing when you look at a patient, whether this is genetic in cause or not.

What is it that directs you?

So that is just experience.

It's like anything and any job.

When you start, you don't know anything.

By the time you've been doing it for 30 years, you sort of know.

And that is experience.

You can't teach it, you just have to do it year after year after year.

But that's the same in any job, I guess.

So after a tough day, then, how do you relax and turn off from the job?

Sometimes you can't.

I've been a doctor for a very long time, and you do learn how to do that or else you couldn't do the job.

As a young junior doctor working in acute medicine, I saw far worse things than I do nowadays, to be honest.

I think that sometimes you just have to take a deep breath and do something completely different.

Get out to the gym or watch something on the television or go out with friends.

You've got to have a life outside medicine, I think.

It's really important, or it becomes all-consuming.

Of course.

So my last question then is thinking of the future.

What do you think the most exciting thing is that's on the horizon that's coming?

I think that we just know about the tip of the iceberg, to be honest.

We think that we do so much more now than we used to.

But actually, all we've done so far is learn how to look at the coding region of genes.

And it's becoming, I think, increasingly obvious that we're a bit more complicated than that.

And that 99% of the genome is not coding region.

And we can sit back and ask ourselves, well, what is turning genes on and off?

How do you get from an egg to a baby to an adult?

It's because of sequential genes turning on and off.

There's a whole regulatory system in there that we know very, very little about.

And I think the answers to some of the genetic questions that we can't answer now are because it's not in the coding region, it's all in the regulatory regions of the genome.

And I think in the next five to ten years, we'll probably start to get a better hold on that than we have now, with a whole new load of diagnoses, hopefully.

Thanks so much to Jackie for joining me on The Road to Genome.

And thanks to you all for listening.

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