Earlier this summer, Young People’s Forum (YPF) member, Annabel, interviewed Mrs Lucy Jenkins, Director of the Regional Genetics Laboratory based at Great Ormond Street Hospital (GOSH). Lucy also works on the 100,000 Genomes Project, an initiative announced by David Cameron in 2012, which aims to analyse the DNA of 100,000 NHS patients.
Can you explain how you came to this role at GOSH?
Lucy: “I started my career as a clinical scientist in the Yorkshire Laboratory in 1992. I moved to GOSH in 2000 to become Deputy Head of the genetics laboratory. Since then I’ve moved up to my current role. I’ve gained the qualifications needed for a consultant clinical scientist role.
“My role is really varied. I’m responsible for making sure all of the work we do is validated and meets all quality standards. It means I get to authorise complex cases before they leave the lab. I also have to make sure we’re meeting our targets as a department.”
What is DNA?
“Everybody’s DNA is different, it’s the code for the way our body is built. It explains why we look different, whether we’re tall or short, have brown hair or red hair – this variation is natural.
“The DNA code is present in every cell in the human body. There are about three billion bases of DNA in every cell. Of those three billion bases, we know what roughly two–three per cent of the DNA is the code for our genes. The other 97 per cent used to be discounted as junk; we are still not certain of its role.
“As a Regional Genetics lab, we look at genes that we know have a function (in the three per cent) and we know that changes in these bits of DNA may cause a disease. For example, a variation in the cystic fibrosis gene may cause cystic fibrosis. Our clinical scientists need to establish if any variation is neutral or likely to cause disease and report these findings back to the referring clinician.”
What’s the aim of the 100,000 Genomes Project?
“What the 100,000 Genomes Project is doing is examining the full genome, the 97 per cent as well as the three percent we already have an understanding of.
“The aim is to sequence the whole genome of 100,000 people. This is roughly split into people who have rare diseases, and people who have cancer.
“When you’ve established a change in the DNA you have to find out whether that variation is likely to cause a disease, or if it’s a normal variation in the patient’s DNA. When you sequence a whole genome, the scientists in the labs here at GOSH are examining these variants to find variations that are significant.
“The idea is that if you get that sort of volume of information from a rare disease or cancer, you can start to look for parallels in DNA changes in people who have that genotype. This might be meaningful as we can begin to develop therapies or define new genetic causes for disease.
“The project started recruiting patients in early 2015 in the 13 centres around England which were identified as genomics medicine centres. GOSH leads the North Thames Genomic Research Centre (NTGMC). Our aim at the NTGMC is to provide around 15,000 samples.
The ultimate aim of the project is to transform the way we look at people’s DNA in the NHS. The idea is that we will be able to send patients to have their genome sequenced as part of their NHS care.”
How does recruitment work?
“Getting consent from 15,000 people is complex. Patients or families have to consent to share their healthcare records for a lifetime. We have to get samples from each person, not just for DNA but additional blood samples for future analysis of proteins and metabolites. We then send these samples to a sequencing facility in Cambridge. If any interesting results are found, we get the samples back so we can confirm them in a clinical setting.
“At the moment our lab has sent about 3,000 samples to the 100,000 Genomes Project. We’ve not had any results back yet but the sequencing has begun.”
How did GOSH become involved in the project?
“We had to bid to become part of the project. We’re a Regional Genetics centre and we had already engaged in the pilot study of this project. We learned a lot of lessons from the pilot, especially relating to the quality of the DNA required.
“One of the main considerations of the project was to ensure that there was geographical coverage of England, so that everyone under the NHS could have access to the project. There are 23 Regional Genetics labs in the UK, 17 in England, who already carry out counselling, DNA extraction and genetic testing. It is these centres that were invited to engage in the 100,000 Genomes Project.”
What are the challenges of the 100,000 Genomes Project?
“Recruitment is a big challenge for us. For each patient we enrol, we need to make sure their parents are willing to take part and that they provide consent for us to have access to their health records for their lifetime. As we’re looking at the whole genome, it’s possible the project will find something that is significant to their health later in life. For example, we might find a breast cancer gene change in a child and the parents would have to decide whether they want that information, should we find it.
“Although the technology around sequencing is constantly evolving, data storage is a big issue. Every time we sequence a genome, we generate around 30GB of data, which is a huge problem!
“Finally, feeding results back into labs like mine means we begin to deliver a genetic diagnosis for our patients. The NHS needs to decide how it delivers genomic medicine in the future.”
How do you encourage patients and families to take part given the lifetime commitment to the project?
“People who often visit an institution like GOSH, where rare diseases aren’t so rare, are usually really willing to help. They want to know what’s affecting their child or causing a condition. Generally speaking, people are proactive and want to provide their details.
“For a child to take part, we’d usually need to take five blood samples. Fortunately, we don’t have to get as much blood from small children.”
What do participants have to do over their lifetime?
“They don’t have to do anything after the original tests. We share the results with them when we get the results back. If the DNA has shown lots of complicated variations, it may be years before a family receives a genetic diagnosis.”
A lot of patients at GOSH have genetic conditions like cystic fibrosis, how will this research change their care in the future?
“It will make a huge difference. A lot of patients at GOSH have very rare conditions and many of those can be attributed to genetic causes, but many of them have not been identified. Once a diagnosis is made, it could lead to fewer invasive diagnostic treatments, like biopsies and anaesthetics. We can also give a family an idea of the likelihood that they may have another child with a genetic condition.”
Where do you hope genomic research will be in 50 years?
“There will always be more to learn.
“When I started this job in 1992, they’d just invented a way to amplify DNA. At the time we said we couldn’t sequence one gene, it was too expensive and took too long. The first exome to have DNA sequencing cost around £2 billion and took a decade. Now it only costs around £1,000 and takes a few days. Genomic research is now an attractive prospect in mainstream healthcare and could be as commonplace as a blood or urine test.
“However, there is still a lot we don’t understand. The more and more data you get, the more you need to find out to actually understand it. It’s understanding the information that’s the biggest challenge to the future of genomic research.
“The next step is to move away from genomic sequencing and look at how the results affect the metabolic system and how proteins are made.”