Improving medicine with 100,000 genomes

David Bentley, who’s the Chief Scientist at the company Illumina, joined Chris Smith in the studio. Illumina is based in Cambridgeshire, they developed the system that we used to read our sausage DNA, and they’re the official partners of the NHS 100,000 genome project. This is an ambitious study unveiled in 2012 by then prime minister David Cameron to read the genetic sequences of thousands of National Health Service patients. David told Chris about the project and how Illumina is involved in delivering it.

David - This project is the first of it’s kind to really examine a large population of patients - 100,000 genomes from around 70,000 patients. And to look in particular at how best to utilise an entire genome sequence in clinical practice; what we can learn from it; what challenges we face; how to handle the information, and how, ultimately, to really make a difference to what is being called precision medicine, or genomic medicine. To give a better answer for each patient because we know about the patient through their genome, and we know more about the disease they may be suffering.

Chris - We did a bit of a sausage in a matter of hours. For those who may be not so familiar with your technology and the technique, how much more of a problem is it to read the entire genetic code of a human in the way you’re proposing to do?

David - The whole human genome of a person is much larger than some of the samples you’ve been talking about. Some 3 billion letters or bases of the genome in every person. And the first human genome, the reference human genome that was talked about earlier that took some 7 years to sequence and an international team to do it.

The technology revolution which spun out of Cambridge here actually allows us to do a genome in about two days. In fact, it allows us to do several genomes in two or three days and that, therefore, really makes it possible to access and provide this information for the benefit of patients in timeframes that are clinically relevant. The doctor can really ask the question and make use of the information, and we return it back in the time that’s really needed.

It’s an ongoing process; it’s accelerating as we go forward and it’s important to say that doing 100,000 genomes is a really big undertaking. It involves a partnership, not just with the NHS but, very importantly, with Genomics England who are set up specifically to manage the whole project, and they partner with us. And they have had to deal with the challenges, not just of how fast can Illumina sequence the genomes? It’s also how can they recruit patients, provide consent, collect samples, return the data, analyse, interpret them, and really get them back to the doctor? That whole process is being tackled straight away at the level of 100,000 over the 3-4 year duration of the project.

Chris - We’re calling this the 100,000 genome project, but there is a subtlety in there because you then said “well it’s from 70,000 people.” So why is there that distinction; why have you got 70,000 people and 100,000 genomes?

David - The project is really addressing two of the forerunner challenges that the genome really hopes to make a big impact on. One is a rare genetic disease which often hits newborns and paediatric conditions. In that case, we really look to try to sequence a child that’s affected and also their parents - that’s three genomes for one disease.

The other important area, of course, is cancer. Cancer is also a disease of the genome but, in this case, it’s the DNA in the cancer which has changed over a period of time. Either through exposure to toxins or radiation, or through other events which have really given rise to changes since the person’s genome was given to them by their parents. Here we’re sequencing that tumour DNA to look at the changes that happened since the germline, since birth. But we’re also sequencing the normal from the same patients so that we can distinguish the differences and really pinpoint what it is that’s happening in the cancer that is not happening in the cells in the rest of the body. That really gives us the clues for what’s caused this cancer; what the person’s been exposed to and, hopefully how we can manage the condition or provide treatment.

Chris - But scientists all over the world have been sequencing genes, and tumours, and patients for a long time, so what does doing this en-mass, in the way you’re doing it, add that other people can’t do and replicate so easily?

David - It’s important to recognise the importance of all those other studies because all that information folds into the present studies. But the key about sequencing the whole genome in one shot, in two days is the possibility gather all the information that might be required. The answer is in there somewhere if you have the whole genome, you just have to know how to find it. You can find the needle in the haystack, but you do at least have the whole haystack to look at quickly and efficiently. We can develop methods, we are developing methods to analyse ever more quickly and precisely, searching through that haystack in a very automated way to look for causes of disease for these particular individuals and provide an answer quickly.

Chris - And how are you getting on; are you on schedule?

David - The programme is going very well. It’s an enormous project as I’ve described. The path from the patient in the clinic right through to the sequencing at Illumina, and back out to Genomic England, and back to the doctor takes some time. We’ve actually done 35,000 genomes so far. The majority of them in the last 12 to 18 months, and we are accelerating the programme all the time as we learn how better to do it. And the teams all over the country from Genomics England to the genomic medical centres, to the research centres, to the data centre are all working together to really decide how best to handle the information quickly and efficiently.

Chris - Just very briefly, David, people often worry when we talk about data, personal data, about data security, so how do you keep a person’s genetic fingerprint safe in your hands or in the projects' hands?

David - It’s important to realise a great deal of effort has gone into the security of individual’s data and their DNA. The chain of custody goes all the way from the doctor and the patient who has consented to be part of the process and has it explained to them. And even by the time the DNA gets to us, it’s been anonymised, so the identity of the person is protected really close to the source and Genomics England take care of that through a high-security data facility. They also store the clinical information downstream to enable people to be secure as they can possibly feel knowing that Genomics England really has the custody of that important privacy and confidentiality of the project.