With the needle in my arm I spoke to the resource coordinator, Sarah Nutland, who has been involved since the resource was conceived six years ago. My initial questions concerned the nature of the data that would be derived from my sample. In particular, I was keen to find out if my full genome sequence would be determined, or if analysis was restricted to more sparse genetic regions (genotyping). Until recently, full sequencing would not have been financially viable, but technological advances now make it a question worth asking.
I was surprised to learn that no genetic information is initially extracted from the volunteers’ DNA. Instead, sequencing is driven by each scientific project. If a research team are studying a particular region of DNA, then that region is genotyped across the panel of samples. The resulting genetic data is used to pool individuals, along with criteria such as gender, age and disease history. Scientists then have the luxury of choosing research subjects who fit their experimental design perfectly.
The power of the resource comes not from the high number of volunteers in each study (typically fewer than 100 people are involved), but from the diversity of the genetic potpourri from which participants can be picked. The bigger the resource, the more likely there will be enough people with the genetic makeup and characteristics required for each investigation.
There is a plan to double the number of volunteers, in part by recruiting patients suffering from a range of long term conditions. Links are being made with disease specialists and a recruitment bus will soon swing into action visiting GP surgeries to harvest donations. It is hoped that the involvement of patients will also inspire donations from their healthy acquaintances, keen to help out.
I have always been wary of taking part in clinical trials, valuing my fully functioning biology too much to risk ingesting pharmacological unknowns. But the types of experiments run by the resource are at a much more basal level. They examine the nuts and bolts of molecular biology, acting more as a prelude to the drug discovery process rather than an investigation of nascent drugs themselves. As a result, volunteer participation tends to be straightforward – in many cases blood and a signature are the only requirements. There are experiments which involve a bigger chunk of time, but participation is always optional. Sarah says that once a volunteer has completed their first study and realise how little is required they are likely to return for another, flush with the glow of donating to a good cause.
At this stage in the conversation the needle had been removed and my two-year-old had fallen asleep on my lap. He had been fussed over by the nurses and was now sleeping off a three-pack of custard creams and a beaker of orange juice the size of his daily fluid intake. As he snoozed, Sarah told me how the resource had been set up.
The lab she was working in, headed by John Todd, was using genetics to probe the biology of Type 1 Diabetes. The experiments needed human DNA, so lab members and clinical staff rolled up their sleeves. When they needed more they asked colleagues in neighbouring labs. Soon it became clear that collection needed a formal footing and BioResource was born.
Ethical considerations underpin the design of the resource and determine which individual studies gain approval. Volunteers are not given any details about their DNA sequence, and only studies where it is ethical to withhold this information are sanctioned. Even the project researchers can only access data tied to their research subjects, rather than across the whole panel of volunteers.
Although no information crucial to the health of each individual is generated, the studies still output genetic data I’d be very interested to learn. For example, a recent paper in Neuropsychologia used the resource to study how differences in the serotonin transporter gene affect the brain’s response to emotionally laden pictures. There are two flavours of the gene’s controller, short and long, your personal combination seems likely to influence how you respond to stress, including your predisposition to depression. Having been touched by the black dog in the past, I’d love to know my serotonin uptake inhibitor type (and I’m not the only one interested). As a rational scientist, I understand that the genetic association is swimming is in caveats and uncertainties, but, on an emotional level, I’d still like to know.
According to the paper’s lead author, Elisabeth von dem Hagen, no volunteers requested the information, and she points out that the pseudo-anonymisation procedure means that the scientists themselves were ignorant. “As researchers, we were blind to an individual’s genotype. It was only once we had completed data collection for the study that the BioResource panel released genotype information to enable us to complete the analysis. At that stage, participants have been anonymised by number so the genotype never gets released together with a name. This procedure also ensures that our data collection and analysis is blind to genotype and can’t be biased in any way.”
As the cost of sequencing falls, I wonder if a point will be reached when it will make financial, logistical and scientific sense to read full genome sequences, rather than running genotyping each time a study is initiated. However, the ethical issues that the resource now neatly side steps will then be unavoidable – what to do with actionable genetic liabilities uncovered along the way. Perhaps by then there will be parallel advances in clinical genetics and everyone, not just those volunteering for studies, will be having their DNA sequenced.
The project has a very Cambridge focus – you need to live near the city not only to donate but also to exploit the resource, physical proximity of subject and researcher being key. (Although if you can’t face battling with hospital parking spaces they will send a nurse to you). The metropolis that is Addenbrookes is very much the beating heart of the resource. DNA sequencing takes place on the site, many of the research groups are based there and Addenbrooke’s staff still make up a significant fraction of volunteers.
Due to the project’s success, bioresource envy is widespread, and Oxford and London are looking to start similar banks. Each would encompass volunteers and researchers from their immediate locality and the three centres could pool samples to enable work on rarer genetic variants.
If you live in the Cambridge area then take the time to visit the BioResource website and browse the wonderful science it sustains. Consider supporting basic medical research yourself - the commitment is small and, at some future point, you may benefit from discoveries made possible by your own unique contribution.
von dem Hagen EA, Passamonti L, Nutland S, Sambrook J, & Calder AJ (2011). The serotonin transporter gene polymorphism and the effect of baseline on amygdala response to emotional faces. Neuropsychologia, 49 (4), 674-80 PMID: 21167188
The impact of a genetic diagnosis
Finding out you are a cystic fibrosis carrier