Posted on 5/10/2018 by

RAREfest: What the public needs to know about about the new science of genetic treatments for rare diseases

RAREfest is set to become the first-ever UK rare disease festival for the public.

The two-day inaugural event on November 30 and December 1 (a Friday and Saturday), organised by Cambridge Rare Disease Network, will see the Guildhall transformed into an interactive exhibition, with talks and films about the much-mooted genetic revolution. The occasion is a chance for those with an interest in genetics to find out and engage with the scientists and researchers working to improve rare disease outcomes.

To discuss the unprecedented opportunities – and challenges – this new era presents I spoke with Dr Anna Middleton, an ethics researcher based at the Wellcome Genome Campus, and a speaker at RAREfest on the Saturday.

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“I’m part of the affiliated staff at the Faculty of Education so we can share PhD students. I don’t do any teaching, but will be supervising our first ‘society and genomics’ PhD student this year, who benefits from a new collaboration between our group and the university.”

Dr Middleton also chairs the Association of Genetic Nurses & Counsellors.

“It’s an association for the 300 genetic nurses and genetic counsellors in the UK. Genetics is exploding into healthcare and our profession will be going through a period of massive expansion – we are the profession that are trained to help patients and other healthcare professionals understand and make sense of genomics.”

Isn’t the NHS introducing routine DNA testing for the first time this month?

Dr Middleton's role includes identifying good practice in the consumer marketplace.

“Genetic services have been in the NHS for the last 40 years, but what’s changing – though it may be slightly delayed – is a new structure to help mainstream genetic testing and create a whole genetic medicine service.

“The plan is to deliver quick, consistent genetic testing results so that, if a patient lives in Newcastle and has relatives in Cornwall, all will get the same genetic testing and the same delivery of genetic information.”

So far, so good – but we’re just getting started. Anna’s day job is head of society and ethics at Connecting Science in the Wellcome Genome Campus. Yet in a Channel 4 News interview she was described as “ethics researcher”. Was that right?

“Yes – though now I’d call myself a social scientist. I don’t do philosophy or ethics as a discipline, it’s a practical role – I’m trying to understand the impact of technology on people. It’s about what they know and what they ought to know. Ethics and genetics go hand-in-hand – and this is because genetic information connects us to our relatives.

“So, you might have a family where some want to know if they have a risk of inherited breast cancer, and others don’t. Or you might have a patient who won’t share their genetic testing results with their relatives, even though this information could potentially save their relative’s lives.

“Genetic information is family information and I’m interested in the ethical issues this raises.”

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“It might seem counter-intuitive, but some of the best genomic practitioners in the world are in the NHS,” she says.

“The genetic analysis is done by the laboratories, and they deliver the results to the clinicians and the genetic counsellor helps to make sense of that data for the patient. For example, if you have patient with breast cancer, a genetic test could reveal whether the cancer is an inherited sort, so you’d then have to think about the relevance of this to your children, and relatives, and what about the other breast? And insurance. And the age of your children – when should they start breast screening? And what about the men in the family – they could be at risk too.

“Genetic counselling is usually for 45 minutes, and we’ve got used to that amount of time in the NHS. With direct-to-consumer they test you for stuff and give you the information and then consider their job is done.”

And that’s bad practice?

“Definitely. It’s something we’ve written about – what’s needed with genetic testing is an opportunity for a proper chat about the meaning of the results, this is what genetic counselling is, that is a real talk with a real person. A lot of companies are offering a chatbox, based on an algorithm.”

A chatbox. The genetic keys to life being interpreted by a machine. I simply can’t compute this information in real time – my brain’s algorithms fail me – so I ask Anna about her RAREfest talk instead.

“I’m chairing a session and doing a talk on big data and genomics. We’ve entered a new era in which we can discuss what data sets mean in a rare disease patient. We need very large data sets. Being able to interpret what a very rare genetic alteration means in a patient can only be done if the laboratory can compare it to the same data collected from other people.

“This way we can work out whether the genetic alteration was linked to disease or health in others – it gives the laboratory a much better chance of understanding how disease might play out in the patient they are testing. These datasets need to contain ethnically diverse mix of people from different ages and backgrounds – ie people around the world need to be willing to donate their DNA and medical data to a global research endeavour.”

Aggregating large data sets means you can find out about prognoses and how treatments work in different continents. From there you can identify other factors – diet, exercise, air quality – which contribute to better outcomes. So: linking up health networks for a global system of genomic data, isn’t that a big ask?

“It means an enormous amount of global co-operation, and industries giving up their data, and that has implications for privacy, and for confidentiality. It means a lot of genetic data bouncing around the internet, and these data sets are precious and require careful handling – they contain our DNA data, it’s more personal to us than an iris scan or a fingerprint. They are also very useful for big pharma.

“The question is, are people OK with pharamaceutical companies making profits out of their data, but then again, this is the way that drugs are developed. I’m interested in altruism: will people give up their genetic data for the good of humankind, or do they expect returns? Genomic medicine won’t be fully realized without global public participation – we need data from everyday people. But why would they give it? What’s in it for them? That’s what I’m interested in.”

Turns out there is another organisation operating in this sphere which Anna belongs to.

“I’m part of the Global Alliance for Genomics and Health, which has more than 500 organisations including hospitals, universities and corporates – a real partnership between non-profit and for-profit industries working in genomics. Google and big pharma are members. It’s about setting very high governmental standards and enabling information to be responsibly shared.”

The Global Alliance for Genomics and Health (GA4GH), formed in 2014, is a policy-framing and technical standards-setting organisation, seeking to enable responsible genomic data sharing within a human rights framework. But has the sector already reached the point where it’s bolting the ethical stable door after the horse has bolted?

“The pace of change is so fast, it takes time for regulatory standards to be set up. With GA4GH, it’s underpinned by a human rights framework. It’s about big data, DNA and the human right that we all have to be able to benefit from science. I’m very interested in the social contract. It’s not enough to say ‘I’m a scientist, trust me’. The public has to be fully part of the conversation – what are the pros and cons of participation? What are the highest standards they should expect from scientists?”

Which is where RAREfest can help. What does she expect?

“My hunch is that it will be aimed at, and suitable for, members of the public who have a rare disease or who have rare disease in their family. We often think of rare disease as unusual, but around one in 17 of us will be affected, so we are likely to know someone with a rare disease. And the vast majority of rare disease is genetic. Rare disease research will uncover causes and treatments relevant to all, so it is massively important and relevant to all of us.”

Anna will be flying back from Hong Kong on the first day of RAREfest after attending the International Summit on Human Gene Editing, which is about putting together global frameworks for the safety of editing human DNA.

“There’s a new technology that allows us to cut and paste genes. The hope is it can be used for treatment of genetic disease. But when you start editing DNA, that’s a huge ethical discussion about what to edit for (what is the difference between ‘disease’ and ‘enhancement’) with potential downstream risks. Lots of genes are multi-function, they could be linked to not just one disease but also to intelligence or other possibilities.”

So it’s possible to edit a gene without knowing exactly how it links up to the whole?

“It uses the self-repair function of DNA, basically. The ‘faulty’ bit of DNA is cut out and the DNA then repairs itself with a healthy replacement.”

What sort of rare diseases?

“Duchenne muscular dystrophy and inherited forms of Alzheimer’s are examples of a rare disease involving a single gene.”

And its functionality can be switched on or switched off?

“It’s more complicated than that: muscular dystrophy, for instance, is caused by a mutation of the X chromosome and the condition is inherited from mother to son. The mums are carriers but they’re not severely affected, nor the daughters – just the sons. The gene has a little bit deleted so you can target that and repair it. That research has been done in dogs and some human trials are just starting.”

And it’s still largely experimental?

“It could affect anything. We just don’t know whether, by repairing it, it affects other functionality. We need to make sure it’s absolutely safe – the technique is to go in and only alter one gene and not other genes, but what are the downstream effects? It’s early days, but it’s looking promising.”

These are topics for RAREfest?

“Yes. What’s most exciting is that genomics and genetic testing is going mainstream. I’m very impressed by the popular response for the festival – and I love the fact that they’re having a film festival as part of it.”

Source: CambridgeIndependent