Dame Stephanie Shirley

2nd International Autism Conference, Wales

Wales' 2nd International Autism Conference,
Autism Cymru


8 May 2006

The Challenges to Autism Research
Dame Stephanie Shirley

Is prevalence increasing? How do we reliably diagnose as early as possible? How do we identify susceptibility genes? Is there one disorder or are there many separate but related disorders? What is different about the autistic brain? How do we apply the advances in neuroscience to understanding and treating autism? How do we share resources and information in an integrated strategy? As regards treatment, what works, when does it work and how do we make it better? How do we optimise current clinical interventions and integrate new research into clinical applications?

* * * * * * *

My Lord Mayor, Minister, Ladies and Gentlemen, Good evening I didn't come to autism, like many parents of a child with autism it came to me, to dominate my life. For 35 years I was involved with the daily experiences of caring, then with support services, schools and various strategic initiatives in the autism sector including – to my pride – Autism Cymru. But, perhaps inevitably, what I do nowadays is focused on research into causes. Understanding the causes of autism will lead to new ways of improving the quality of life for all those affected. I work through Autism Speaks the international charity that recently amalgamated with the National Alliance for Autism Research and I chair its UK affiliate.

Once when I was a child, I found myself lost and frightened in a park. Then, quite by chance I came across one of those maps on a notice board with a big arrow pointing, "You are Here". Awesome! How did they know? In research, we start from where we are, identify some landmarks and then follow a path to where we want to be in the future.

I finally got my own notice board with an arrow on it. My charitable Shirley Foundation commissioned a global review of published material on research into the causes of autism. This work by Dr Jenny Longmore and Kate Egan is now being submitted to The Lancet. My acknowledgement underlines how often we need to work cross-discipline. Cross-discipline, inter-disciplinary, multi-disciplinary. The living sciences are always crossing borders. And it may seem obvious but it's funny how often we forget to talk to one another. My first piece of advice to the researchers here is to try not to duplicate what has already been done. And publish what you do do. It can be important to know that something didn't work and, as James Joyce put it, "mistakes are the portals of discovery". So publish or perish.

Researchers can take comfort in the title of my presentation the Challenges to Autism Research. For the flipside of any challenge is an opportunity. There seems to me to be seven of them. They call on different skills so there is potential for each of us to have the beautiful but frightening excitement of being the first to know something.

Nobel Laureate Richard Feynman wrote in 1996:

"The worthwhile problems are the ones you can really solve or help solve, the ones you can really contribute something to. A problem is grand in science if it lies before us unsolved and we see some way to make a little headway into it."

When my beloved Giles was born in 1963, autism was considered a rare disorder. To distinguish it from mental health issues, we have learnt to call it a disability but either which way perhaps the most significant challenge to the autism research community stems from the apparently rapid increase in the number of people with autism. Worldwide a new case of autism is diagnosed nearly every 20 minutes. So rapid an increase in numbers as to explain autism's poor funding and the unacceptable waiting times for services. So the first challenge to autism research is to account for this change properly. Certainly the face of autism has changed, but no one knows whether the increase is due to more sensitive measurement; redefinition; or (the more disturbing possibility) a true increase in the disorder. (Exactly the same queries that arose when the numbers for schizophrenia rose rapidly in the nineteenth century).

We know so little about autism. It's a major obstacle to progress that diagnosis continues to rely on behaviour rather than basic biology. So the second challenge: is how to reliably diagnose autism and as early as possible. Children with ASD are not all the same. How can we reliably distinguish between different patterns or stages of Autism Spectrum Disorder and related developmental problems? How do we separate the developmentally delayed ("boys are always slow in talking, Mrs Shirley") from the disabled; and the disabled from the more specifically autistic. This issue confounds many experiments having control groups of typical children whereas what is needed is subjects with similar mental capabilities, epilepsy or whatever, but without autism.

But there's little doubt that there is a strong genetic component. The unravelling of this is one of the greatest challenges we face. If only it were as simple as the genetic variant marking an increased risk of prostrate cancer (the most common cancer among men) that I read about this morning. Many people have emphasised the need to obtain genetic samples of carefully diagnosed and characterised subjects – families in which there are several affected individuals, ideally over several generations. It's likely that gene identification will require thousands of families. We also need a global, standardised autism twin registry. The third challenge to autism research is to answer that very question: is there one disorder or are there many separate but related disorders or alternative expressions of symptoms? Instead of working with apples and oranges, we want to be able to work with different strains of apples, eventually just different apples. I referred earlier to ASD but perhaps the different autisms should be considered in a 3-dimensional space not just on a spectrum.

How do we identify the susceptibility genes? I am reminded of Agatha Christie's "Murder on the Orient Express" where no single person was guilty; they were all guilty, together they killed the victim. Of course, I use the term guilty here metaphorically – no gene is guilty – it is no one's fault. I know how corrosive blame is because in the early days of autism the mother was blamed for the way the child developed. And there are still worldwide remnants of such thinking, even in central Europe. So how should we approach our task in different societies? We fail to distinguish core attributes if actually they are cultural. Asian cultures consider eye contact to be impolite, for instance; and some questions used in diagnosis ask about children's response to their birthday party – a celebration not practised in many parts of the world. I am recently returned from Saudi Arabia where the consanguineous marriages make the gene pool particularly rich for research. Autism Speaks signed a Memorandum of Understanding with the Prince Salman Center for Disability Research. It is demonstrably not enough to refer to (as Muslims do) people with autism as being "exceptional" and with a "developmental disorder".

I pose the questions but do not have any answer.

And what do all these genes do anyway? What are they doing to the brain? Which leads us to our fourth challenge. To learn to apply the tremendous advances in neuroscience to understanding and treating autism. What is different about the autistic brain? The susceptibility genes act by modifying the development of neural systems. Imaging technologies have made a tremendous difference to neuroscience. But progress with children with autism has been slow. This is partly because imaging children requires a level of compliance and patience, sometimes difficult even for normal adults, much less vulnerable children. Imaging technologies (or it could be methodologies) that worked for children with autism would significantly advance our understanding of their altered information processing.

An extension of this challenge four is that the few existing brain banks provide only limited tissue of quality and access; progress is hampered by the shortage of post mortem brains – either from those with autism, or for use in control groups. Researchers have my son's brain. And they'll have mine. Human brains are the world's most precious resource. The cost of brain banking has come down, down, down, so it's largely staff costs: to administer the registrations and make best use of the actual donations (all the while being compassionate and professional throughout the grieving process). You may like to know that Autism Speaks planning meeting for an Autism Tissue programme in Europe was held in January attended by those involved in the States, several UK brain banks and researchers and members of the autism community from the UK, Ireland and France.

Challenge five comes back to my own discipline of information technology where my business succeeded because I was able to bring people (actually women) together. How do we bring resources and information together in an integrated strategy? The Human Genome Project involves scientists from all over the world networking together to share resources, data and technologies. Similar strategies are probably necessary to address the complex biology of the brain. This work has already begun in autism research as people work from centres of excellence and multi-site, international programmes scan for susceptibility genes. Speaking again from my own profession, can I mention the power of information technology in drawing together data sets and mining down for their secrets. This is now happening with Phase One of the international Autism Genome project. Early indications are that (and I quote) three or four new genomic regions harbouring autism susceptibility genes have been identified. And importantly there has been independent confirmation of two previously detected linkage signals. Watch this space!!

Early on I mentioned my change of focus from intervention to cause. Which brings me to the sixth challenge.

As far as treatment goes, how do we optimise the current interventions and integrate new research into clinical applications? It's important to have a concerted and vigorous effort to benchmark interventions, perhaps tailored to unique sub-sets of autism populations. The lead charity, the National Autistic Society is planning a major drive in this area. So is the American NIMH, an outcome of the collaboration between biomedics and educators in recent years. I'd comment that interventions are typically applied when children are pre-school or already in school – relatively late. Studies of the infant siblings of children with autism can effectively allow interventions for very young children (by which I mean under 3 years). As early as 9 months has been reported.

Those people with autism whom you have seen, or know, or love, stand for countless millions around the globe, often in circumstances more abject that we are ever likely to encounter. I'd like to emphasise translational research. Advances in brain research which translate into meaningful clinical applications deliver answers and solutions to the community. And that, surely, is what we are all about.

Perhaps because I had a traumatic childhood and so experienced at first hand the vulnerability of the child, I feel so strongly about what I consider the supreme challenge of autism research. My final Number seven challenge is the vulnerability of children during research, their inability to make autonomous decisions, (I understand legislation in Scotland is helpful with this issue) and the absolute right of affected families to confidentiality during the research process.

Thoughtful strategies to address these important issues must be integrated into every step of the research process. It's necessary (but not sufficient) for professionals to avoid confronting children much as they do a laboratory specimen. And particularly with children with autism – each is neither a miniature adult nor just a walking set of conditions. Paediatric ethics depends on genuine respect for children – not always easy! We need to distinguish between child assent, parental permission, legal authorisation and moral responsibility. And we must learn to listen to parents. A research worker may aspire to become a world expert in some aspect of the science. But most parents already are world experts in their own children. Parents are needed to play both formal and informal roles in the research process. The worst thing paediatricians can do is to ignore parental accounts of their children.

It's useful to remember that most funding for research comes from the public sector. Autism Speaks is mounting a Parliamentary lobby to increase the funding for research into the causes of autism – part of an ongoing lobby to redress the disproportionate low spend in this area – compared with less common disorders. And to move autism up the agenda – permanently – in both the UK and in Brussels.

There has been enormous engagement of the public in issues such as MMR. Much of it has been misguided, hysterical, unhelpful. But it has engaged the public. And you need to engage the public because, let's face it, we are only one research area among many competing areas. It would be good if practitioners could also become activists and promote getting more money for research.

I try to work always with respect. Respect for people with autism who, like my late son, are without speech, epileptic and with profound learning disabilities. Also respect for those high performing individuals at the other end of the spectrum who denounce my search for causes because autism is a natural part of the human condition. Some people believe that everything that's natural is good (people with religion refer to divine will). But flu is also part of the human condition and, excluding the minority groups who resist any form of medical intervention, most of us use antibiotics to fight the virus. Certainly autism is a very specific way of being a person.

Let me once again encourage talk. Gone are the days when findings arose from the lone scientist isolated in the laboratory. The most successful scientists are team workers. A recent study of Nobel Laureates found that they collaborated with colleagues more often than the non-prizewinner scientists who worked competitively. So I believe that the basis of real progress in our sector will come when people work cooperatively rather than competitively. Partnerships, alliances, associations, affiliates, consortia, networks – these are the workshops of the 21st century.

Congratulations to Autism Cymru and all success to this important conference. Let me finish Chairman, with two aspects of timing. My age gives me an urgency you youngsters lack but I have learnt "Urgent Patience". For research cannot be hurried. No matter how much money is allocated, the search for causes will still take years. But there are times when things are moving and times when they are not. There is a paradigm shift in medicine generally so be assured that there is a timeliness about autism research today. Science is always the art of the possible. And if researchers work, with the respect that I spoke about at the beginning, on the main challenges to autism research and don't just tinker round the edges, there are very good chances (perhaps as high as 1 in 10) of producing something that makes a real difference.

Oh, how I wish I were starting again.

Copyright May 2006

Dame Stephanie Shirley

Tel: +44 (0) 1491 579004
Fax: +44 (0) 1491 574995
Email: steve@steveshirley.com
Website: www.steveshirley.com

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