Every month, one member of the TGMI team will tell us why they are so committed to the vision of the TGMI, and share a bit more about their work and interests.This week we hear from TGMI Programme Director Nazneen Rahman.
What has been the main focus of your work to date?
I have worked as a scientist-clinician in the field of genetics for 20 years. Genetics largely passed me by at medical school (I was either rowing or singing!). But when I started as a PhD student in Mike Stratton’s group, just as he was discovering BRCA2, I was immediately seduced by the beauty and power of genetics. I’m still captivated.
I started my own research group at the Institute of Cancer Research, London in 2001. For the first decade, my group did disease gene discovery research. We have been particularly successful in identifying cancer predisposition genes for breast, ovarian and childhood cancer. We also work on rare genetic syndromes, particularly those that lead to increased growth.
Over the last five years, my group has expanded into more translational research and clinical implementation. In part this was stimulated by my taking over as Head of Cancer Genetics at the Royal Marsden Hospital. I could see, first hand, what could be achieved in genetic medicine if one was purposeful.
This led me to set-up a clinical gene testing lab, TGLclinical and two integrated science-translational-clinical programmes in genetics. The first is the Mainstreaming Cancer Genetics (MCG) programme, which has changed the paradigms in gene testing for cancer patients, to make it integrated into routine cancer care, more patient-centred and more cost-effective. We are so happy at how well that is going. The second is the TGMI.
What are you most excited about in genetic medicine?
Affordable gene sequencing gives us the opportunity to massively increase the scale and reach of genetic medicine. For most of the last 25 years, access to genetic medicine was, necessarily, limited. Now we can, and should, strive to use genetics wherever it can provide health benefits. Across the world.
The range of different ways in which genetic medicine can be usefully deployed is vast. When I first started in genetics I never dreamed we would get this opportunity during my career. I feel really lucky and really excited.
What are you most concerned about in genetic medicine?
Unfortunately, incorrect use of genetic data in medicine is rife. Many people are in ‘catch-up’ mode, trying to adapt to the new knowledge that large-scale genetic sequencing has provided and to the new interpretation paradigms that large-scale, broad-brush clinical gene testing has mandated. This is leading to widespread misinterpretation of genetic data, which in turn can lead to misdiagnosis and to mismanagement. The potential harms at the individual and societal level are very worrying. Sometimes it keeps me awake at night.
Why did you get involved in TGMI?
There are two main reasons, one professional and one personal. The professional reason is that I felt a strong responsibility to step up at this incredible time in genetic medicine to try to deliver on the potential benefits and to minimise the potential harms. The personal reason is that from the moment it became clear there are only 20,000 genes (previously it was thought to be many more) I have had a recurring fantasy of going through each one to work out whether mutations in the gene cause a genetic condition. In building the Gene-Disease Map for TGMI, I finally get that chance. I believe many scientific and clinical insights will follow from this endeavour. Watch this space!
What is the most important thing that you would like the TGMI to achieve?
If we can realise our ambition of a standardised system for annotation and reporting of gene variation, I will be very, very happy. It’s a much more complex task than it seems and will require us to be both innovative and very persuasive!
If you had a magic wand (i.e. unlimited people/resources) what would you do to make genetic medicine work?
I’d love to set up a global genetic testing system for rare childhood genetic syndromes. It’s not as fanciful a dream as it might seem. And everyone would win.The testing would be paid for centrally so children anywhere in the world could benefit. The testing for poorer countries would be subsidised by the richer countries. But the richer countries would also benefit hugely because they would have access to much more data which would greatly improve interpretation of their tests. Interpretation is a major bottleneck and error point in genetic medicine currently, so this is an important benefit.
For ultra-rare genetic conditions a global system makes the most sense. One of my TGMI collaborators Sian Ellard has more-or-less done this for neonatal diabetes. It can work!
Do you have a favourite gene? If so – what and why?
I’m rather prone to having crushes on genes. Every gene I’ve ever known is more intriguing than it first appeared and I get briefly enamoured by their complexities. The mysteries of KNL1, HIST1H1E and DNMT3A are diverting me at the moment. I have to confess I’m feeling guilty about not saying BRCA2, with which I have a passionate, but dysfunctional, long term relationship!
What is a surprising fact that few people know about you?
I’ve sung for Stephen Sondheim. He won’t remember. I won’t forget.
If you had a chance to experience a completely different career for a week, what job would you try?
It’s not exactly a different career, but I’d love to be an eagle for a week. I have an unquenchable yearning to fly. It’s led to some near-death experiences over the years!