008 - Getting ready for genomic medicine

Kat - Hello and welcome to a special edition of Genetics Unzipped, The Genetics Society podcast, in association with the Genomics Education programme - part of Health Education England. We’ll be finding out how genomic medicine is coming into the NHS, and what it means for everyone working in the health service.

Since the publication of the draft sequence of the human genome back in the early noughties, researchers and doctors have been working hard to harness the secrets within our DNA in order to benefit human health. Progress was slow for several years, due to the high cost and slow pace of sequencing technology. Everything changed with the advent of Next Generation Sequencing in around 2009, making it possible to read the entire sequence of anyone’s genome at low cost and high speed.

To realise the potential of this technology in healthcare, the 100,000 Genomes Project was launched in 2012 aiming to sequence - as you might have guessed - 100,000 genomes from people affected by cancer and rare diseases within the NHS. The next chapter began in October 2018, when NHS England launched a brand new Genomic Medicine Service, using insights and information from the new era of large-scale DNA sequencing, known as genomics, to improve the nation’s health. The service is aiming to sequence 500,000 whole genomes over the next five years, as part of the UK government’s broader aims to reach five million genomic tests by 2024.

I spoke to Bill Newman, Professor of Translational Genomic Medicine at Manchester University - over a slightly dodgy Skype connection - to find out where we’ve come from, where we’re heading, and how genetic testing could make a difference to healthcare.

Bill - I think is interesting to look back at how the 100,000 Genomes Project was first set up and it had a number of different goals and a number of different ambitions. Some of that was to provide some equity of access to genetic testing across the whole country - we know that some patients were able to access certain types of genetic testing and other people maybe with the same condition weren't able to.

There was a discovery part of the work to try to identify new genes or new types of changes in genes that could lead to different health problems, and that's going to be an ongoing project for a number of years. And I think it was to try to link together a number of different elements of the health profession and the public and patients. So there was a whole education program to increase both health professionals’ and the public's knowledge about what genomics was able to do what it was able to provide.

Kat - That brings us up to where we are today because we've seen the 100,000 Genomes Project wrapping up and this new genomic medicine service starting. What's the real focus of that? Where are we starting from? Because it's I think it's very exciting to say, oh we could do all of this, we could look at loads and loads of people's genomics we can do all of this. But where are you deciding to start?

Bill - So I think there are a number of different starting points. For the 100,000 Genomes Project the actual sequencing part of the project has finished but there’s still a very large amount of work to do to try to provide answers for a number of the participants. We've been successful in providing answers for some of the people that took part in the project and that's been excellent, but still lots of work to do to try to ensure that all those people that took part and we don't have an answer for yet, that we continue to look at the data and try to identify the specific cause for their health problems or maybe changes in genes that are relevant to their diagnosis of cancer.

I think it's trying to take that knowledge from the 100,000 Genomes Project about where the biggest diagnostic uplift has been - where is genomic sequencing really making the difference. One of the focuses as I’ve said right from the outset with the 100,000 Genomes Project, which is really being taken forward through this new service, is to ensure that there's equitable access for patients irrespective of where they live so that they can get access to the most appropriate genetic testing for their clinical needs.

Kat - I know that the initial focus of the genomics medicine service is going to be cancer so testing people's tumours if that's appropriate and trying to select may be the appropriate treatment for them. But I'm sure you know as well as I do that cancer is a lot of different diseases and many, many different types and there are many, many thousands of people diagnosed every year in the UK. So are there particular areas where you're starting to focus particular types of cancer, for example?

Bill - There are a number of tumour types where understanding whether an individual has a particular genetic change can make a real difference to their treatment. And so lung cancer, melanoma and bowel cancer -  colorectal cancer - are three major areas where genetic testing is already in place. One of the aims of the Genomic Medicine Service is to ensure that all of the people with those different types of cancer are getting the right testing in a timely way that can inform their care.

Rarer tumour types like childhood cancer and sarcoma, which account for relatively small numbers, but, at the same time, I think that whole genome sequencing has a lot to offer to identify genetic changes that might inform specific treatment.

Kat - You mentioned rare diseases as well. What sort of comes under that banner and how could genomic testing actually make a difference for these kinds of people?

Bill - So we know that there are approximately 8,000 rare diseases - rare disease is defined as affecting less than 1 in 2,000 people. The vast majority of such rare diseases have a genetic basis, it's either a change in a person's chromosome pattern or in a single gene, and we know the causes of over 6,000 of those rare conditions.

And so for a person who has a rare disease, an organisation called rare disease UK show just a few years ago that for an average patient it takes somewhere over five years before they get a precise diagnosis. That can mean lots of going to different doctors, lots of investigations, lots of uncertainty. Once people have got a specific diagnosis, then that information can be used to inform the right clinical care, the right screening that they might require, and it can provide certainty about how the condition came about and what the risks might be to other family members.

Kat - Bringing this kind of new approach into the NHS seems like a massive challenge as well as a massive opportunity. What do you think are some of the biggest challenges that are facing the staff that are going to have to deliver this new kind of medicine?

Bill - I think one of the biggest challenges is the scale of what we're trying to achieve. A lot of what we're setting out to do we understand some of the processes what it involves, we know that it is possible, but to deliver it in a timely way and to the numbers of patients that such testing will be appropriate to is a real challenge.

And so looking to some of the ways that we need to streamline that will involve much better informatics, much better support through computing systems, linking different centres sharing information and allowing us to analyse the data that we need to.

And then there's a really big education piece that needs to be done to ensure that all the health professionals that will be using genetic testing really understand when it's appropriate to use that, how to interpret the results and for professionals like myself in genomic medicine that we give the right support to my colleagues in paediatrics and oncology, in different areas of medicine, so that they feel that they're able to use the genetic tests that they need for the benefits of their patients.

Kat - As Bill mentioned, one of the main focuses of the Genomics Medicine Service is cancer. To discover more about the applications of genomics in cancer, I spoke to Dr Alison Berner, a clinical research fellow in medical oncology who is using data from the 100,000 Genomes Project in her research at the Barts Cancer Institute in London.

Alison - There's a number of applications to the changes that are driving cancer in the DNA. One of them, and the one that people are most interested in, is can we target those changes to the DNA with specific drugs and one of the ways that the 100,000 Genomes Project has been amazing for patients is that it's enabled us to identify patients who are eligible for clinical trials of new drugs where we wouldn't have known that previously.

However, there aren't that many ‘Magic Bullets’ in terms of being able to target specific mutations and Cancers get resistant really, really quickly. So another way that this might be applied is to use a number of different drugs targeting a number of different pathways and that's why having a whole genome sequence rather than tests of individual genes is really useful.

Kat - The people that have taken part in the 100,000 Genomes Project have they had access to these kinds of very targeted drugs?

Alison - Most patients who have been part of a 100,000 Genomes Project haven't had a specific drug matched to their cancer. But the reason sequencing their genome is useful is that by building a bank of cancer genomes, we can infer things about different subtypes of cancer, and we can also think about things like prognosis which is really important to patients.

Another thing that's really important to happen is what happens to cancer tissues when we take them out of the body. It used to be that we put them in a chemical called formalin, which preserves them really nicely and you can just store them in a box at room temperature, but it really damages the DNA. It makes it really difficult to do sequencing

For the 100,000 Genomes Project we stored the tissue fresh and then froze it, which sounds really simple but actually if that's quite difficult to do quickly and NHS hospitals weren’t geared up for that. There's still a lot more work to be done to do that anytime of the day or night so that if you go in as an emergency with your cancer, we make sure we can still sequence your genome and don't bias you just because you had your operation in the middle of the night.

Kat - We've been able to look at DNA sequences from people and from cancers for a little while. What has that information being used for so far in the clinic? Where are we now with using what we can get, what kind of information we can get to improve treatment for patients?

Alison - So up until now we've looked very separately at the two different genomes involved in cancer. The one that most people think about with regard to cancer treatment is what we call the somatic genome, so it's all of those DNA mistakes in the cells that have led to cancer. So far we have tested either for specific DNA mutations and changes or for limited numbers in panels and tried to match patients to drugs using those.

The other genome that we look at is the germ line, which means the DNA changes you inherited from Mum and Dad. There are a limited number of cancers that tend to run in the family as it were, so you might think about Angelina Jolie and the BRCA gene, for example. By knowing about those changes in patients with a family history, we can allow them access mainly to additional screening or perhaps surgeries to prevent them developing cancers in the organs at risk, but sometimes there are specific treatments that are more effective in those patients too.

Kat - Let's drill down a little bit into what you said. So where we are at the moment, we take the sample of a patient's tumour, we look at certain genetic changes and say OK, we have these drugs and these tests and so we can match you up if there's something that works in there. What's the future of that? Because obviously we're missing a lot of information and a lot of opportunities. What do we need to do in the future to make this better? What's happening now?

Alison - So that's one of the reasons that we want to do whole genome sequencing, as we've done in the 100,000 Genomes Project, for all patients because we can look for changes across the DNA - n genes that we know to cause cancer, in genes that we're just finding out will cause cancer, and in other genes that might affect they how well you respond to a cancer treatment, even if they're not driving your cancer in the first place. So we get a wealth more information.

There are also bits of the DNA which don't code for any particular proteins. They sort of affect what levels of other proteins there are, and this DNA which we call non-coding is actually really important in cancer too and by sequencing the whole genome we'll learn more about that and might be able to target that in the future too.

Kat - So it feels like at the moment we've got a picture where maybe there's a big painting which is our understanding of cancer and how to treat it, and the moment we've just looked at tiny little patches and spots and go, oh, that looks like a nose or a flower. So I guess with whole genomes and genomics we can see start to see the whole picture and pick out what's going on?

Alison -  Yes. So by looking at these hundreds of thousands of genomes, we can start to pick out that information. And really right now it's over to the researchers to gain new insights from these big data sets, and then once they've done that allow us to use that information in the clinic.

So now that the 100,000 Genomes Project has come to a close and become the NHS Genomic Medicine Service, we aren’t actually going to sequence the whole genomes of every single cancer just yet because actually it's too much information and we don't quite know what to do with it. We are sequencing the whole genomes for cancers where there's a big need, like those in children or those with cancers of the blood for example. But for other cancers, we are going to use the best amount of information that we have and work towards using whole genomes in the future.

Kat - Yeah. That's an interesting point because it does seem there's a lot of excitement around this everyone is very excited about genetics and genomics lots of stories in the media the idea that you'll get all your genes looked at and we'll know exactly what to do. So we're not really there yet?

Alison - No, it's not an exact science and I think what the media might not put across is how much this is still very much research. Even when you send off for some of these DNA tests that are advertised which looks at your risk of developing particular conditions - you can swab your cheek and send it away in the post - actually what that gives you are tiny amounts of information about a possible increased risk. It doesn't give you certainties, because the complex nature of our DNA means that every gene is affecting every other gene. So there's still a lot of work to be done.

Kat - What do you think are the key things that people need to know about where the science is now and where it's probably going to be heading in the near future? If you could say, “Right, the main thing you really need to get about this science is this.”

Alison - I think what you need to understand are there are some changes to DNA that very clearly cause cancers and drive cancers, and some of those are important for how likely you are to develop a cancer, how serious it will be, or whether we've got a particular drug to treat it. There are some other changes to the DNA where we're not quite sure the effect it yet, and we have more studies to do with more people to work out what subtle changes those genes make and whether they're going to be useful for treatment in the future.

Kat - So it sounds like there's a lot of exciting changes on the way making this a reality. What are some of the misunderstandings and maybe misconceptions that you've come across when you're talking maybe to patients or to even clinicians or people who work in the healthcare service about where we are and what's coming down the pipeline?

Alison - One really important distinction to make is that difference that I spoke about to do with hereditary changes causing cancer and changes that are happening just in your cancer cells which are driving your cancer. So it's important to understand that just because we've said you’ve got a DNA change that doesn't mean that other people in your family are at risk.

Another really important distinction to make is that just because you have a particular mutation in your cancer, that the drug that targets that mutation is definitely going to work because as I've kept saying it's not so simple and every gene is affecting every other gene. There's no Magic Bullet and we can't guarantee what is or isn't going to work always.

Kat - There’s a lot of excitement within the health service and among patients about the potential to use genetic and genomic data to improve outcomes and extend survival, but we’re a long way off a place where these treatments are available to all. So it’s important for all healthcare staff to think about how to handle what might be difficult conversations with patients about such a complex and new area of medicine, as Dany Bell, apecialist advisor in treatment and recovery at Macmillan Cancer Support, explains.

Dany - I think the conversation is really important. I mean, it's a very difficult time for people, they have high anxiety levels, all the research shows that they don't hear everything in a consultation. So I suspect the conversation has to be layered and it has to be a phased approach.

You've also got the implications that if they don't have the gene. So how do you balance it to not raise expectation at the front but then introduce a conversation later on when you've got all the information and can actually have a real dialogue about the treatment and how to best treat them.

So the conversation for me is really important, and I guess again that has two implications because it's the implication for the person around the tumour and depending on the genetic output from that is then the hereditary risk for people that are their nearest and dearest, and now that again has a real emotive impact. So I think managing the conversation and support that person needs is going to be vitally important.

Cancer professionals, specialist professionals are used to having difficult conversations with people and so will have some skills around that. But I would say probably a lot of the workforce are not prepared for these types of conversations because obviously we're now moving from what was research into mainstreaming into pathways. So, you know, it may be challenging and we may not have all the answers which is why education and all the things that Health Education England doing are so vital really.

Kat -  What do you think are some of the really problematic terms and concepts. We say whole genome sequencing, exome this and that, targeted mutation blah blah blah blah blah. What do you think are some of the terms that we should be aware of that can trip people up or cause confusion?

Dany - I think I think those types of terms in reality will confuse a lot of people - it will go over their head. They won't understand and you know finding a language - one of the things that we sometimes do is when there's difficult subject matter, we help create a narrative. So I quite like the idea that it creates a blueprint to help the the doctor to target their treatment and the treatment that's right for them.

I mean you can use the word gene and you can use the word genomics but I think all of that other language will be lost on people, although there will be some people that understand it. We know that people have varying levels of health literacy. But I think if you can have a common language that you use for everyone and then if people are asking for more detail, then that's fine. But I think it's probably fair to say that a lot of the mainstream frontline cancer professionals and then the wider workforce like GPs, they won't even be using that language and they won't understand it. So it's better that they find a language that's comfortable for them.

Kat - This idea of using genetic information to inform healthcare, it is very new. Do you think the Health Care Professionals, doctors, nurses, other people working in healthcare are actually really prepared for this and they have got their heads around it?

Dany - I don't think so, in all reality. I think when you move something that's been predominantly in a specialist arena as a research project, where perhaps a small number of the front line workforce have been involved, then you won't have that that spread and awareness right across the workforce. There has been a massive amount of work done for the future workforce, but in a sense I think we're probably playing catch-up with the current workforce.

But it's not unobtainable in the sense that it's a phased rollout. So it's just about targeting different areas of the workforce and supporting people to embed it in pathways, to know about the conversation, help them have the right conversation, have the right information resources to help them support people.

One of the things that we find really helps if you have some written resources that are then backed up by conversation. Then people can go away and reflect on that and they've still got the leaflet or the information about genomics.

Kat - And what do you think the main messages are that patients, the public, healthcare professionals need to really understand about genomics - that shared language, the shared ideas that we're all talking about and we all get?

Dany - I think the key thing is for them not to be frightened by it. It sounds very fancy language – genomics – but actually, it's a really positive thing and I think it will enable their team to know how to find the best treatment for them. And I think that is the biggest positive message.

Obviously, you've got to manage expectation. But actually, you know, we are in a different arena with cancer treatment than we were 20 30 40 years ago. So I think that that is a really positive message.

Kat - You mentioned managing expectations. Are there any misconceptions that we need to deal with when we're thinking about this area?

Dany - So I think from the patient's perspective, for it to benefit the person there needs to be a gene identified, there needs to be a treatment for that gene. And so for those where a treatment has not been developed or they don't actually have a particular gene then I think that's quite difficult.

I think professionals will need support in how to have the conversation about that expectation because people will saying why can't I have that treatment? They'll be sitting in a clinic area and they talk to each other and somebody will be on a very different treatment pathway to others. They'll go on online communities and blogs and read things, and they'll be thinking why not?

And so it's getting the information across that they understand why they can't have that particular treatment, but equally for the professional, even if it does identify things it still may not give them all the answers. So it's kind of a work in progress, isn't it? It gives us better information and we can have better options in thinking about what sort of treatment options are available for someone. It just may not give all the answers all the time, but it's absolutely a massive step in the right direction.

Kat - Is there anything that would particularly help in terms of making this vision of genomic medicine a reality here in the NHS?

Dany - I think all of the key organisations that are stakeholders in health and care - and that includes Royal Colleges, universities and the charitable sector - they need to kind of own it and recognise what it means to the people that they support.

Kat - And finally do you think there's almost a watchword or just a concept that healthcare professionals should be bearing in mind when they're having conversations that are based around these new frameworks of genomics and using genomics to inform healthcare?

Dany - Simple is always best. It's the best way to help people understand. Just use simple language and explain it in terms that they would understand if they were on the receiving end of it as well.

Kat - Simple may be best, as Dany says, but being able to explain something well really starts from our own understanding. Dr Anneke Seller, scientific director of the Genomics Education Programme, told me about the challenges of embedding genomics in the NHS, and the resources and training available for all staff as genomics moves towards the heart of modern clinical practice.

Anneke - So there are many challenges because we have a 1.3 million workforce, it’s very diverse and it's very, very complex. Everybody needs to know something about genomics, but what they need to know depends very much on their role and their function within the Genomic Medicine Service and in with the wider context of the NHS as well.

Kat - So give me some examples then. Say, what would a doctor or a clinician who is dealing with a cancer patient, what would they need to be thinking about and be aware of?

Anneke - A clinician, say dealing with a cancer patient, needs to be aware of what sort of testing is available for their patient, what genomic testing should they be undertaking to inform the diagnosis and the treatment and the management of the patient, and from 2019 onwards whether the whole genome sequencing might be relevant for their for their cancer patient too.

And so what they would need to know is something about the test directory that we have, which specifies all the different tests that are available both across cancer and rare diseases, and this is new for cancer in the NHS. They would need to know how to consent their patient for the genetic testing and whether they wish to participate in research as well.

They would also need to know enough genomic literacy to attend the genomic medicine MDT for that area and to talk about their patient from a genomic perspective in that environment. And they would need to be able to understand the genomic report and to navigate their way through all the different terminology and look at the actionability of what's in that report. And then of course, very importantly they need to be able to communicate those results to their patients.

Kat - So that clinicians - doctors who are dealing directly with patients. What about other people who are working within the healthcare services - things like nurses or genetic counsellors. What other sort of things do people need to be aware of?

Anneke - Nurses are critically important for us in the Genomic Medicine Service because patients trust nurses and they talk to them. So all nurses need to understand something around genomics so that they can have that conversation with patients. But we also need specialists nurses who have genomic counselling skills, who understand something about the genomic report, who get involved in in the feedback of results to patients as well.

Kat - And are there other people working within the NHS who will need to know about this or actually think, oh you need to skill up and tool up a bit?

Anneke - Absolutely. It goes across the board and we haven't mentioned the laboratory staff who are very key in undertaking genetic tests. It's not like all of this is new - we've been doing genetic testing for many, many years - but many aspects of it are new around the technology and the bioinformatics. Especially within the cancer field we need to upskill staff in this who work in those laboratories in particular around genomics and histopathologists as well.

Kat - And what sort of resources are you providing as the Genomics Education Programme to help these different audiences and to really help people in the NHS get to grips with this this Brave New World of genomic medicine?

Anneke -  We work very, very closely with the professional bodies and with the professions directly and we always consult with subject matter experts when we're developing our resources, and we provide a range of resources for everyone effectively.

So we have short online courses, which can be readily accessed through our website, and these courses provide an introduction to genomics perhaps. We've also got course that shows how to take a pedigree and draw a family history. We've got courses explaining what genomics is and how it is applied in healthcare.

But we also have courses that are geared towards the more highly skilled professionals. So for example, we've got a competence based tool for histopathologists and biomedical scientists to learn more about how to assess a tumour sample for suitability for DNA extraction looking at neoplastic cell content, for example.

Kat - And how would you like to see this progressing over the next few years as genomics becomes more embedded? What would you like to see happening and transforming in the workforce?

Anneke - So what we'd like to see in terms of the education and training is that it is very much linked to their career pathways - that they can do elements of training that they can see that this adds to their career. So it's credentialed - it's part of, for example say, nurses that it’s as part of an accredited clinical practice or an accredited scientific practice. So we'd like to see those elements.

We want to see a really comprehensive range of education and training so that people can step on and step off, that they can access just when they need it. And we know everybody in the health service is time-poor, they need to be able to access their learning in the way that they want to at the time that they want to do it. And so we need to have resources that are readily accessible online, and we also need to bear in mind that face-to-face is often quite a useful medium for learning and for training and education too.

Kat - More generally, what is the sense within the NHS in England as we move towards bringing this new technology to patients? What are the hopes, the fears, the challenges - what's the vibe?

Anneke - So there is huge excitement I think across the whole of the NHS system, not only in in the frontline, but also in the wider NHS system like NHS England, Public Health England, Health Education England as well. I’ve certainly heard from colleagues of mine that genomics is the best thing that's happened to them in their career and think it might be the best thing that happens in the whole of their career and I think this exemplifies how exciting this development is.

But there are challenges and many people are concerned at the pace of change that were going through at the moment with this and the implications that this has for safety and the quality of the work that were undertaking.

Kat – Obviously we've got the NHS workforce that we have now, but there's the next generation to think about - people who are considering a career or going into training, whether that's in medicine or other aspects of healthcare delivery. What are the challenges and the needs there?

Anneke - So there's plenty that we can do with the prospective workforce, and we actually do need to start off in schools looking at the A-level curricula, looking at how we describe careers in the health service in genomics so people are interested in becoming a doctor or a nurse in genomics, but also particularly in bioinformatics - that's an area that we really want to recruit people from school to think about a career in the Health Service rather than a career in gaming. The skills are very, very similar so actually we just need to entice these people into the NHS! So that's one area that I think we need to focus on.

The second area is looking at the undergraduate curricula that we already have for medicine and for nursing and for healthcare scientists, and making sure that genomics runs throughout those curricula, that it's up-to-date and modern and it's not just taught in a silo in one particular module at one point in their training or their undergraduate learning.

Kat - So genomics is for life, it's not just for one term before Christmas?

Anneke  - Absolutely! I think genomics is for everybody and it's across the board, yes.

Kat - I couldn’t agree more! Thanks very much to Anneke Seller, Dany Bell, Alison Berner and Bill Newman, and also to the Genomics Education Programme and Health Education England for sponsoring this special episode. If you’re a healthcare professional and want to know more about the resources and training in genomics that’s on offer, please head over to www.genomicseducation.hee.nhs.uk – and you can find the Genomics Education Programme on Twitter @genomicsedu for all the latest news and updates.

For more information about this podcast including show notes, transcripts, links, references and everything else head over to geneticsunzipped.com You can find us on Twitter @geneticsunzip or email us at podcast@geneticsunzipped.com with any questions and feedback. Please do take a minute to subscribe on Apple Podcasts or wherever you get your podcasts from, and it would be great if you could rate and review - and more importantly, please spread the word.

Genetics Unzipped is presented by me, Kat Arney, and produced by First Create the Media for the Genetics Society - one of the oldest learned societies in the world dedicated to supporting and promoting the research, teaching and application of genetics. You can find out more and apply to join at genetics.org.uk  Our theme music was composed by Dan Pollard, and the logo was designed by James Mayall. Thanks to Hannah Varrall for production, thank you for listening, and until next time, goodbye.