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The Genome and Medical Matters: Edited transcript of a presentation by John Forman to the 13th World Congress of Inclusion International, Melbourne, 23 September 2002.

Thank you Kevin for your introduction, and greetings to all of you from all over the world.  I would like first to acknowledge the aboriginal people as the first people of this land. Now I will make a couple of comments about what you see on the first slide. I have the double helix from DNA as the background because I think, whether we like it or not, it has been in the background of our lives for many years, it has a very significant impact, and I think we need to be reminded of its significance.  Also, that while I am a member of the Hutt Valley Branch of IHC, and I have a number of other roles in that organisation, these views are my own. 

In this presentation I will take the approach of talking about our experience by introducing myself and the family.  I will look at how knowledge of the human genome and modern biotechnology has great implications, I believe, for intellectual disability.  I will discuss some conclusions and as some of you may expect, I'll offer a few challenges. 

I'll talk first about myself and my family because I believe that, in order to know where we are going, we need to know where we are and in order to know that we need to know where we've come from.  You've probably all heard that jargon expressed in various ways and I think it is very important to stress that my knowledge comes essentially from personal experiences plus the learning that I have built on top of that experience, to be able to look at things in a wider context.

About me. I'm the parent of 27 year old twins, both of whom have an intellectual disability.  I've  had quite significant involvement in IHC for many years and I have various roles in it, and in associated organisations to do with the disability sector.  Those are my many volunteer roles.  Then the things I have done for a living. Perhaps going back to roles in the Public Service and as a Firefighter in the 70's is not quite so relevant to this discussion.  What is perhaps more important is the 7 years that I spent working as a Manager in community support services for people with mental health disabilities and my current role as the Executive Director of NZORD - the New Zealand Organisation for Rare Disorders.

This next slide is me and my wife Judith and our son and daughter, Timothy and Hollie.  And our story I guess could be traced back, well, prior to their birth as we have an x-ray there from 3 weeks before they were born.  I'm not quite sure if it shows too clearly but what you see is on that day of 23rd October 1974, one of the first surprises was to discover that there were two little ones, rather than one large baby.  Of course this is the days before ultra sound.  See how technology changes our lives. You will be able to see Tim's head engaged there and the spine curving back over to the left and Hollie curled up on the top there. That was the first of many surprises, but the result was these two beautiful babies (and that photo was taken at about 15 months of age).  I want to introduce them now and let them say hello. (Video clips of Timothy and Hollie).

As you can see I am a very proud parent and it is hard for me to get away from the personal, but I think we should not try too hard to do that.

The key issues for us in the early years were all about inclusion.  After adjusting to the reality, there were some quite significant chronic health problems (ENT, respiratory, dental) that needed to be dealt with on an ongoing basis but getting support for our family to manage and getting a place for them in society - in kindergarten, schools and so on - were the key issues for us.  But in the teenage years other problems started to emerge.  There you see an x-ray of Hollie's hips and her left hip which is on the far side of the screen there, shows a very seriously eroded hip joint.  Our response to this was:  "All this and arthritis too - what's going on and what have we done to deserve this", but other things happened in the teenage years as well.  We got all of these other things including an accurate diagnosis at last, the realisation it was a progressive disorder, there was an increasing health component to their disability and we understood more about what was actually going on.

By now we had a changed understanding of what we were dealing with.  We understood that their disability and their health problems resulted directly from an identifiable genetic problem.  But things got more difficult as time went on.  You see there the x-ray which shows the result of the failed hip replacement operation. There were a number of other problems which carried on through their teenage years, including joint inflammation and ataxia.  Again, our understanding developed to the point where we knew that all of these things were the direct result of the genetic problem, of the medical condition that they had, to the point now as 27 year adults we have a different view of things that we had at the beginning.  We now know that they are affected by a medical condition which is well described in the literature, although it was not back then, that it is now treatable by bone marrow transplant if it is diagnosed early enough, and quite likely it will be curable in the future. 

And so to Conclusion #1.  I think we all need to take another look at how we see the relationship of medicine and society to disability.  What causes disability, what perpetuates it and what solutions there may be to reducing the level of disability and to promoting inclusion in society?

If we go back over that period of time just described and put it into a time line, we see from the time of their birth we had a certain set of issues to deal with, with inclusion a major one.  From about 1990 onwards, management of significant health issues took over from inclusion as the key issue for us and that actually raises one of the key questions that I have for the whole of the disability sector. That is, is real inclusion possible when there are major health issues to deal with? 

Let's look at the same time line with a different set of data in it. At around about the same time, 1990, was the development or the start of the human genome project.  In 1993 was one of the first developments in significant policy with governments deciding they wanted to know more about cause and effect of these rare disorders and they wanted to learn more so that they could have the potential to do something about them. This was the establishment of the Office of Rare Diseases in the United States and then a few years later I put the internet at 1996 because while it was around before that it was not widely available to ordinary people - you had to be an enthusiast or an academic to have access to the internet much before then.  And so knowledge was changing and people's access to knowledge was changing dramatically.  So what we had throughout the 90's was an increased understanding of the causes of disability and for many disorders an increased capacity to intervene through a variety of means, including biotechnology. 

The times they are a changin'.  At a personal level the change in Timothy and Hollie's health and disability status went hand in hand with a change in our knowledge about it and the change in the access that we had to information and networks.  And I am suggesting that at a societal level also there has been significant changes in the knowledge of many conditions that actually cause intellectual disability.  There is a change in the ability of medicine to intervene.  There is a change in health research which has changed the relationship of the scientists and the doctors to those who are the participants, patients, or research subjects. And there is a significant change in patient and family knowledge and networks about many conditions.

Conclusion #2. The world has changed and the knowledge of these things has changed whether we like it or not.  We are facing a paradigm shift - in other words, we need a whole new way of looking at things and there are a lot of challenges for the disability sector to meet.

Lets have a look at one of the issues that I think we need to address.  We've talked for years about the medical versus the social model and I don't want to say much about the medical model other than that that we know it was the thing which led to institutions, and while it may have provided some useful and needed services at particular times when no alternatives were available, I haven't much else to say about it that's positive. But I do have a question.  I wonder if in fact the medical model really was a social model of exclusion in disguise.  I'll just leave that for you to think about - I don't have time to discuss that any further.  But lets play tribute to the institution for just a brief moment - good riddance to it. 

Let's have a look at the other side of the medical versus social model.  The social model essentially says: We're all okay as we are and society's barriers create the disability. My argument is that that rather simplistic model is not adequate when you are dealing with a disability that is clearly disease driven, especially those that are severe and degenerative. I think that social model thinking is relevant to the 70's and 80's, where it did fit with the progressive social thinking that was predominant at the time, and the clear limits of knowledge and technology that was dominant at the time. But in my view it contains some quite deafening silences. 

Conclusion #3. We need a model that ties all these issues together. That integrates understanding the biological causes of disability, with greater capacity to prevent or reduce disability, with the vital aspect of inclusion. I think it is important that we have a balanced view, not just one or the other.  We don't want everything totally medicalised. We don't want things segregated. We don't want inclusion considered solely, at the expense of avoiding treating treatable conditions.  Now that new model could be called anything you like I guess, but the most important thing is that whatever model we have, it must deal with all of the issues.

Reality check number one.  Now have I jumped a bit quickly to a few conclusions?  Can you see the writing in the middle of this cartoon?  "Then a miracle occurs" and the person is saying, "I think you need to be a little bit more explicit to step 2 here".  So let me take a few moments to look at some issues relating to genome knowledge and when I talk about genome knowledge I'm not just talking about the identification of single genes and their function.   I'm talking about all of the associated biotechnology. That may not be describing it perfectly correctly but for the purpose of the discussion, I'm talking about all of the data and all of the technology that goes with it.

The cell. I am sure many of you have seen diagrams of this before, with the genetic material, the DNA, in the nucleus of the cell and various other pieces like the mitochondria which people would have heard of - the engine room of the cell - and the lysosome down there which is the recycling centre, the exhaust system I guess you could call it, and those are things which enable the cell to function.  If we dig down deeper and go inside, you will find in the central region of the nucleus the chromosomes and they have been talked about on many occasions and are reasonably well understood as to situations where faults or errors in those actually cause an intellectual disability.

But the great increase in the growth of knowledge, has been about the fact of extending those chromosomes out and understanding what is happening, or what those chromosomes actually consist of. That is, when they are unravelled you get this beautiful DNA helix which contains within it the genetic code for the person. The diagram on the left shows this extension and that is what the computers in the Human Genome project have been busy reading, the 30 or 40 thousand genes, to try and identify what they are, what their function is, and what they do. The other diagram shows how those four chemical bases, which are repeated in a variety of sequences, make up the gene. When you get those in various combinations, in various sequences, you get a gene which is a recipe which tells the cell when to produce certain proteins, what protein to actually produce and when to stop producing it. 

In that rather truncated and perhaps simplistic overview of the biology and the genome knowledge that comes out of it, what it suggests to me and I think is reasonably accurate to say, is that if disability is not caused by an accident or an environmental factor, it will result from one of these defects in the genome or in the cell structure or in the chromosomes. So you will get mitochondrial malfunction, lysosomal disorders and so on which are sub headings under the general heading of genetic disorders.  These will lead directly to the condition that causes the disability.

Now most of them are in fact single gene defects.  An error in the genome means that the recipe doesn't work properly and the protein which should be there is either absent, or there in the wrong quantity, or with not quite the right characteristics, and that leads to specific problems.  This series of letters is one way of representing it.  There ought to be a T as in the top line but there is a C as in the bottom line and as a result of that rather incredible little detail you get a significant disorder which may result in an intellectual disability, described I guess as nature's spelling mistake, or God's spelling mistake, depending on your personal view.

Of course the knowledge of this does raise options.  It may be that from this knowledge we can do something about it, or, we may be able to discover ways to do something about it. Here are some of the options - repair or replace the gene, replace the missing protein, transplant stem cells to correct the defect, or produce some targeted drugs to compensate and manage the symptoms.  So the human genome project is essentially about speeding up the gathering of this knowledge for all of the genes in the genome.  The biotechnology gives new options, at the same time as the computing power has allowed that knowledge to come together faster.

But there are issues about society's reaction to new technologies.  There is debate and concern in the community and the disability sector in particular about the genome project and the implications of all of this knowledge.  And I suggest that what we need is some careful analysis, research, and so on, rather than knee jerk reactions. 

Now let me offer you some brief analysis of my own in relation to a number of different disorders that do result in intellectual disability.  I will talk in relation to these once again using 1990 as the critical time, for what I am about to speak on is the progress in the knowledge and the development of treatments since that time, and the approach that has been taken by the family groups, for those with the particular disorders.

Fragile X - and this is since 1990.  The gene was discovered.  Conceptual models of how therapeutic approaches might me developed have been undertaken in research laboratories and the family support groups have been very supportive of that research because they want it to happen.

Hurler Disease - a disorder which a much shortened life expectancy - a very severe disorder often leading to very severe disability.  The gene was only discovered in 1991, but thanks to a commitment by a particular family who put up the money to allow a researcher to continue with his work, an enzyme replacement therapy is in clinical trials and it is expected to be approved within the next six months, and Hurler is represented by this photo of an Aucklander, Joseph Eskrigge who died from this disorder at 2 years of age. 

Hunter Disease - I put up the reference to Gargoylism as a reminder of the inherent repression and discrimination that there has been in society for many years.  This disorder is often very distressing for the person and for their family, yet as a result of research, and support from family groups for that research, a treatment is coming to clinical trials. And here I acknowledge Greg Rice, a young man who died at age 18 from Hunter Disease. 

Sanfilippo Disease - another condition which involves severe neurodegeneration. Sanfilippo Disease is always fatal, often in the teens or sooner. The research is very strongly supported by families and I am talking about foundations which raise millions of dollars and support major research efforts for this disease and a variety of related diseases because they want the treatment and they hope for a cure. Joanne Freigard shown in this montage of photos, has defied all the odds by surviving until age 34, profoundly disabled now and probably in the last year or two of her life.  The condition is usually fatal at a much earlier age. 

Tay-Sachs Disease - again a very limited life expectancy with profound disability.  One of the efforts that were undertaken by the family support group was to develop a carrier detection and prevention programme which was set up by the Tay-Sachs Family Association in 1970 and the families give very strong support for the research into that disorder.  The photos show Thomas Lord and Cameron Lord, first cousins who were both affected by this inherited condition and who both died at about 2 years of age.

Rett Syndrome - the most common cause of intellectual disability in females after Downs Syndrome and Fragile X.  Where are they all, who's identified them all, or failed to do so?  Perhaps there's an awful lot of people with autism who have not been correctly diagnosed. This particular condition was a total mystery until the first medical article was published in the English language in 1984 and there we see Kristin Deane with the classic hand-wringing feature that goes with that disorder and I don't know if you can tell quite from the photo that she is holding her breath which is another one of the characteristics. She died at age 26.  The gene for this disorder was discovered in 1999 and there is a significant amount of research going on strongly supported by the Rett Family Association to try and figure out a way to reactivate the gene which is silenced, which does not perform the function that it ought to and has it lead to a protein imbalance. 

Prader-Willi I don't have a photo of, but many of you will be aware of this condition.  There is now a genetically modified growth hormone treatment available which is reported to significantly improve appetite control, leading to better body mass and improved general health and improved socialisation.

Adrenoleukodystrophy - An X linked disorder.  Some of you may have seen the film "Lorenzo's Oil" which made this condition quite famous.  It has severe neurological damage. A significant amount of understanding about that disorder and considerable efforts towards research and possible treatment, came about because one family put in a tremendous collaborative effort with the researchers to try and understand it, and there is a photo Augusto Odone who is Lorenzo's dad, photographed with me when we were both presented with an Advocacy Award by the Genetic Alliance in Washington last year.

There are many other rare diseases which cause intellectual disability.  Hundreds, probably thousands of them.  Knowledge of cause and effect is growing, there is an increasing potential to intervene and research is advancing steadily in the area of gene therapy.  Some animal models have been successfully treated with gene therapy to restore some cognitive functions. 

Conclusion #4.  The biotechnology and the genome knowledge offer potential for much improved quality of life and that's probably what I want to put a circle around as one of the main reasons why I am advocating this line, because I am on about the quality of life of those that we support and those members of our families.  Perhaps those who would actually benefit could well be more than 50% of all the people who have an intellectual disability, and it is important to realise that families do not give up hope and once they know why, they want to know when, and this presents a few challenges. 
" There is not enough informed debate going on to ensure that there is understanding or acceptance.
" Will we take the steps to ensure that many more of them reach their potential?  And I've added there, because that's what we can do for PKU and for hypothyroidism which you know, for several decades now have been identifiable early, and have medical interventions to prevent and control the intellectual disability that would otherwise be inevitable.  A totally different outcome because of medical research and intervention.
" And are we adjusting out thinking and our policies to meet these new possibilities. 

I want to go back now and take another look at the issue of community reactions.  Here's a cartoon which is 200 years old and it came from a major anti technology movement, the anti-vaccine society, at the time that the smallpox vaccine was being developed.  There were riots in the streets of London because people thought that all sorts of terrible things were going to be done to them. In fact that disease has now been eliminated from this planet, and many others such as rabies and hopefully soon polio, will be going the same way as a result of looking how we can intervene medically to reduce disability and improve quality of life.

Back to the Paradigm shift - or "Back to the Future" perhaps. I want to look briefly at how the New Zealand Government policy deals with these issues.  Now there are three main strategies relating to disability - the New Zealand Disability Strategy is the overarching one and there are quite specific ones about mental health and about aging.  If you look first at the policies on mental health and positive aging, they both take an integrated approach to the health and the disability of the person and there was specific rejection in the age care sector of the concept of separating health issues from disability issues.  The New Zealand Disability Strategy in referring to the rest tends to use the jargon - the under 65's - to cover everything else that's not mental health and not age related. There are some very important issues dealt with by the disability strategy.  It covers some issues very well but I believe it is poorly informed about health issues for people with disabilities and it needs to recognise a wider range of needs.  Now what would that range cover? 

At one end, those who are in fact in reasonably good physical health who are not sick but do have an impairment and need access to health care when ill.  A social model of disability - that's what I read for that group.  At the other end, high health needs, disability clearly disease driven, and it needs some diagnosis, some research and some treatment.  I think that we need to have integration in health and disability issues for those at this end of the spectrum, a very substantial group, because most conditions will have potential for improvements in quality of life and a reduction in the disability burden, as a result of all this new knowledge and technology that we are getting. The New Zealand Disability Strategy needs to develop an integrated approach as it already has in the other two areas of mental health and positive ageing.

Conclusion #5. This is essentially saying that better health makes inclusion more possible for disabled people.  And if we fail to acknowledge that and to act on it, I believe that we will be doing a serious dis-service to many severely disabled people. 

More Challenges for the Government and the Disability Sector.  When these issues are discussed in condition-specific or disorder-specific or disease-specific groups (take your pick - I use the three words interchangeably), the response from patient and family groups is strong and clear.  Overwhelmingly it is: do the research, develop the treatment, find the cure and provide prevention measures.  Will we support this approach to allow more people with disabilities to reach their potential?

But what about values?  We can't consider these issues without taking this very important issue into account.  What is the implication for this for values and what are the ethical issues that arise?  I can't do a detailed analysis of this, but I will use one example.  I'll go back to the issue of carrier testing, pre-natal diagnosis and pre-implantation diagnosis; because they are the ones which tend to sound the alarm bells ringing for many people.  If you look at the literature in the disability sector about these, there is some very, very strong language.  There is talk about "new eugenics" and there is frequent comparison to things like Hitler's genocide.  There are claims of discrimination and calls for laws to prevent these approaches.

Let's look at the specific example of Tay-Sachs - you remember the two first cousins I showed in the earlier slide.  It's a condition which leads to severe intellectual disability - it is always fatal in infancy and in one particular population there was a very high carrier incidence. Their Family Association set up a carrier screening and prevention programme in 1970.  By 1998 they had screened 1.3 million people world wide and one set of figures shows there was a 90% reduction in the incidence of Tay-Sachs amongst families in the United States.  In other words nearly 600 fewer babies born with that particular condition over a 28 year period.  If we think of that as one of these uses of the technology in practice and what the implications are, and think about that in the context of literature talking about eugenics and Hitler's genocide -  who was the population?  Ashkenazi Jewish.  Jews of German and Polish ancestry. I think that is a very significant fact.

So what about values?  At a personal level we have no problem at all - we see no contradiction whatever - in unconditional love for Timothy and Hollie yet reserving the right to have chosen to avoid a repeat in a second pregnancy if that had occurred.  And at a societal level we see no contradiction at all in valuing and including all disabled people, yet taking as many steps as possible to reduce the incidence and the severity of disability. 

There are challenges in particular I believe for those who are academics in the disability sector about how they write about these issues.  I want to convey to you a message that many families are deeply wounded by the language that is used.

Some more challenges. Will we assist these possibilities to become a reality, because if so we will need major commitment over coming decades?  We will need to be promoting research, implementing treatments, expanding newborn screening and early intervention programmes and supporting carrier identification and genetic counselling, alongside the vital work of valuing and including all disabled people.

Conclusion #6. I think it is important that we must take maximum advantage of the genome knowledge and biotechnology and by doing that we will show the greatest respect for both the family and the individuals affected by intellectual disability.  It will empower them, it will give them real choice, it will free them from their inner-most constraints and enable more of them to reach their full potential. 

And Conclusion #7 is really flipping that around and saying that if we fail to do that it would be a serious breach of our responsibilities and it would be unethical of us to deny the benefits to families and to people with an intellectual disability.

I will finish in the way we finished our presentation to the New Zealand Royal Commission on Genetic Modification. It addresses the issue of who speaks for whom, as well as the benefits to be gained. We said:

We state our case for those now gone
whose silenced grief and pain spurred the quest for answers;
For those still living
too few this mighty power will comfort;
For those yet to come
whose lives may be transformed.

We rest our case
For those who cannot rest theirs.

And now some acknowledgements. To my wife Judith, and my son and daughter, Timothy and Hollie. Special thanks to Gillian and Roderick Deane who have been very supportive of the work I have been doing on these issues. And to Francis Collins, head of the US arm of the Human Genome Project who allowed the use some of his slides. Thank you.