Rafael J. Yáñez-Muñoz

Our first 2016 Q and A is with Rafael J. Yáñez-Muñoz who runs the AGCTlab at Royal Holloway, University of London and organises the annual Rare Disease Day event that we attend.

When and why did you first decide you wanted to be a scientist/clinician?

I was blessed with my Biology teachers at school in Madrid; 35 years on I still remember them and count them as friends - Alberto de la Cruz and Alfonso Pérez Legido. They taught me how scientific research is done and made it sound attractive. At the time of making university choices, I was interested in Medicine, but not in practicing it, so I chose a degree in Biology, and specialised in Biochemistry and Molecular Biology. For most of my five year degree (1982-1987), I did unpaid work as an intern in two different labs simultaneously (working any spare time not devoted to lectures, lab practicals, or basketball. My fellow intern and school friend Manuel Serrano and I, unknown to us, were called “The Dynamic Duo”, after a Spanish pop group famous at the time). During the specialist years of the degree I developed an interest in evolution, particularly at the molecular level - looking at how DNA changes over time due to natural mutations. Some research groups at the Molecular Biology Centre “Severo Ochoa” attached to the Biochemistry Department were world-leaders in evolution of viruses, which are easier to study and evolve very quickly. In the last year of my degree I secured a PhD with two of them, and soon after I finished I got Scholarships to fund my studies. My first DNA result as a PhD student is still in my family photo album (I am oldish, so I still have pre-millennium printed photo albums!). The rest is history…

How did you come to work on SMA?

Scientific research is terribly expensive and essentially only funded work can be undertaken. In 2006, just before I joined Royal Holloway, University of London as an academic, I was looking for diseases to which I could apply some safer gene delivery system that I had developed as a junior scientist (believe it or not, the system is based on HIV and is great). A fellow Spanish scientist told me about a Spanish consortium in the making, to be devoted to research on Spinal muscular atrophy. They welcomed me to join the proposal as an “out-station” in the UK (the other 15 groups were in Spain), and to our delight our GENAME consortium was funded by a Spanish government agency and the Spanish SMA charity, FundAME. That was my first major grant and I could never thank them enough.

Talking about funding (sorry, I cannot help myself), there is an SMA project I am very keen on and have not yet managed to get funded – not because of lack of interest by the relevant charities, but because of lack of funds on their part. It is a bit of a departure from my usual molecular biology fodder, we have entitled it “Ethical and social issues in perinatal gene and cell therapies for Spinal Muscular Atrophy (ELSI-SMA)”. Briefly, this project would (if we find the money!) explore the views of patients and professionals on the use of experimental gene and cell therapies for Spinal Muscular Atrophy during pregnancy or shortly after birth. The possible use of these therapies on unborn and newborn babies is associated with many ethical and social issues, and very little is known about how these are viewed by families living with the condition. Through the use of interviews and a survey, we will address this gap in understanding, and provide recommendations for future therapy research. The project is a collaboration with a colleague from Warwick University, Dr Felicity Boardman, and another from Holloway, Dr Afsane Riazi. We are seeking funding for a PhD Scholar to carry out the work under our joint supervision, and Royal Holloway has kindly committed £30,000 if we can find the remaining £54,547 of our proposed 85K budget. This would pay a PhD student stipend for three years, and all associated costs (student fees, a lot of travel to interviews, focus groups meetings, and so on – I said research is expensive!).

What would you be if you weren’t a scientist/clinician?

I think I can safely say that I would not have taken a 9-to-5 job. One of the aspects I love of research is the flexible life that it lets you have. In my case, it has allowed me to spend time with my children when they were growing up, see them at events or support them in a way that otherwise I could not have done, and visit my family in Madrid frequently over the 21+ years I have been here.

Answering your question, when I was in secondary school there was nowhere near as much career information available as there is now. Had I known that I could have trained as a medic, and followed a research path afterwards, I would have probably chosen that option. As a non-clinical scientist, if my research moves on to clinical trials (and I sincerely hope it does one day), at some stage in the clinical translation process I will have to hand over the reins. That is not necessarily what one wants to do after working on a therapy for many years.

If you are not in the lab or seeing patients you are...

I have two children, one now at university and one in secondary school. For as long as I can remember, most of my free time has gone into ferrying them around to school and their activities. However, I like to keep reasonably fit, and find ways to sneak out to the gym a couple of times a week.

Describe yourself in three words:

Committed, resilient, approachable. All critical to the way I understand science.

What has been the most important moment of your career so far?

When I (leading a team of 17 people, science rarely is a lonely endeavour) demonstrated that our engineered HIV variants can be used to deliver a gene and thus treat a disease in rodent models. This was published in Nature Medicine, a top-journal, cemented my career and was probably critical for me to secure my first academic appointment at Royal Holloway.

What is your most memorable finding relating to SMA?

It is still unpublished but should not be long. We have a method to deliver a gene with high efficiency and specificity to motor neurons in the unborn rodent foetus. We hope that this may eventually develop into a therapy for SMA, allowing treatment of the disease before it wreaks havoc in the unborn child.

What is your favourite conference location?

There are many but one is particularly close to my heart. I have been a member of a number of EU-funded consortia (yes, one more of the many positive aspects of EU membership, please do not get me started on Brexit – I am hoping to write a piece on that soon), and for one of them, called PERSIST, we held our yearly meetings in Leukerbad, Switzerland, in January. They were really intense but I always spared a little time for a lovely mountain walk in the snow.

What is the best scientific advice you ever received?

The best advice was not verbal but through example: my PhD supervisors in Madrid, Eladio Viñuela and Esteban Domingo, gave me the support and freedom for me to take responsibility, make my own mistakes and find my own space. Other mentors treated me likewise later in my career, and that is something I try to return as a supervisor: I encourage people to take responsibility and find their own way.

If you could start your career all over again, are there things you would do differently?

I would try to make fewer mistakes!

In your opinion, what makes a good scientist?

A scientist must be curious by nature; if you do not ask yourself the questions, you will not find the answers. Having said that, I must go back to the three characteristics I alluded to before: commitment, resilience and approachability. Science is for the most part a 24/7 career path, although with great flexibility. It is extremely competitive (there are very few stable jobs for research scientists and academics) and full of disappointments (most grant applications are not funded, most research papers submitted for publication are initially rejected and require further work and resubmission(s) before they are finally accepted). And you have to be able to communicate successfully with and attract funders, good job applicants and students, colleagues and the wider society. Sound scientific training is critical, and it should include more management, accountancy and communication skills than it currently does.

I know this sounds hard, and it is. However, nothing beats the feeling of looking with trepidation at the result of a difficult experiment and realising that it has worked – AWESOME.

Where do you see the SMA research field in the next 10 years?

The on-going SMA clinical trials are incredibly exciting. I really hope that in ten years-time we have at least one marketed SMA therapy implemented in the clinic and we are working to make it better. We will learn loads along the way – that is science.