Our genomic DNA comprises a sequence of base-pairs, arranged in triplets from any one of four different bases labelled A, T, C and G. It holds the blueprint for production of all the proteins which control the structure and function of our bodies. Differences in our DNA sequences are the reason for many of the differences between us, including our susceptibility to disease. Today, there are a wide range of genetic tests to identify specific DNA sequences that are associated with disease. To take us to the next level in understanding the role of genetics in our health, in 2012 the National Health Service in England started a program for whole genome sequencing.
However, this revolution in health began relatively recently, with the development of new technology that allowed small fragments of DNA to be sequenced. It was around this time (late 1980s) Professor Sir Michael Stratton, then a recently qualified junior doctor training in histopathology, started to carry out research into cancer. I spoke to Professor Stratton to understand more about his work. “The world down a microscope is one of great beauty”, he started, but he was eager to join in on “the molecular biology revolution” that was beginning to emerge. His first steps were faltering. He described himself as “utterly hopeless” at the start, but perseverance and luck led to some “interesting results”, and the offer to start his own laboratory at the Institute of Cancer Research. Some remarkable genetic discoveries followed.
He led research into susceptibility to breast cancer, discovering the BRCA2 gene, in which mutations predict high risk of breast cancer. This is one of two key breast cancer susceptibility genes. Since their discovery, he estimates “probably hundreds of thousands of women have had the tests” for mutations in these genes, which “hugely empowers” them to “make choices about their lives”. Undoubtedly this has benefitted many women, who may now choose to have a prophylactic mastectomy, lowering their potential risk of breast cancer by 95%.
As Professor Stratton and his team sought to make these discoveries, he describes having “a separate segment of (their) lives which (they) spent thinking about what the ethical implications” might be. He remembers having “questions about what to do about it if you found you carried a mutation of BRCA2”, because at that time “there was an awful lot (they) didn’t know”. For example, they could not even be sure whether “if you removed their ovaries and breasts prophylactically, their risk of cancer would drop”. Moreover, people questioned “how could you even offer the possibility to a woman to mutilate herself by removing her breasts and ovaries”. Professor Stratton reflected that frequently, there is a conflict between what “an individual might want” and “what society might tolerate”, and how discussions have to take place to decide what “society will licence (a) woman (with high risk of breast cancer) as a set of choices”. Professor Stratton recalled that “a lot of different groups were consulted in those discussions... not just doctors, but the Lay, patients involved in a particular disease, lawyers and philosophers”. These discussions “allowed society to feel as though it is monitoring and exercising restraint, while people who are really affected feel like they have had their voice heard and that the system is working on their behalf”.
But what does the future hold? According to Professor Stratton, “there’s no test quite like sequencing a genome”. He speculates that “prenatal testing and detection of cancer are areas where very large-scale genome sequencing could well be with us within a decade”. Currently, all children have a series of tests for genetic diseases when they are born. However, with new technology, we “can actually more or less get rid of all of those tests and replace them with a genome sequence”, simply by taking a blood sample from the mother at six weeks, and could “significantly reduce the number of people with these disorders”. At present, this will involve the termination of foetuses with certain genetic diseases and consequently requires further ethical discussion on a case by case basis. But in future gene editing may prevent the need for termination. In the field of cancer, genetic sequencing not only offers the possibility of “a test that detects almost all types of cancers early”, but “a sort of personalised medicine” to treat them, leading to better outcomes.
On a final note, Professor Stratton turned to the rest of life on earth. Our world is “faced by the threats of climate change that we have thrown at it”, so “it seems like a reasonable thing for us as humankind, to make a complete inventory of all the living organisms on earth” by using the genome of each species as a sort of “barcode”. In time we may be able to “use natures tool kit in unimaginable ways”.
By Lucia Noursadeghi
