Friday, 31 May 2013

How do Parkinson's researchers discover new knowledge? Part 4

Part 1:

Part 2:

Part 3:

TOOL 3 – Expression plasmids

To understand a gene you must understand the protein it generates; the criminal has to be investigated to understand the extent of his crimes.

What does the mutated protein do?

Genes contain the information required to build proteins; genes are said to “express” or manufacture proteins and they can do this because different combinations of DNA subunits link together specific amino acids, which make up proteins.

Is it possible to express the mutated protein to help study it? Researchers use necklace-like circular DNA molecules called expression plasmids to express genes. First a gene is copied by PCR and then inserted into the expression plasmid (like adding links to a necklace). The expression plasmid is transferred into cells where it tricks the cell into expressing the gene it carries.

TOOL 4 – Green fluorescent protein

In every cell proteins are busy carrying out all of the essential functions needed to keep the cell alive. Different proteins work in different areas of the cell; imagine a cell is like a house and each room requires different furniture and appliances. If a protein is to be understood one of the crucial things to know is where in the cell it does its job. Normally, when you look at cells down a microscope they are colourless so how do we pin point one colourless protein out of thousands in a cell?

A special protein found in jellyfish called green fluorescent protein (or GFP) glows green when a particular wavelength of light is shone on it. By following the green glow you know where GFP is. Can this help locate other proteins? GFP is expressed from a GFP gene and, like all genes, the GFP gene is made up of A, T, C and G subunits. This is important; it means that a gene from a person (e.g. the gene we found mutated in the Parkinson’s family) can be attached to the jellyfish GFP gene to form a hybrid gene and therefore a hybrid protein: one half human and the other half jellyfish. Therefore, wherever the human protein goes the GFP protein goes too; when an expression plasmid containing the GFP hybrid gene is introduced into cells a particular part of the cell will glow green, demonstrating the human protein does its job there.

Thursday, 30 May 2013

How do Parkinson's researchers discover new knowledge? Part 3

Part 1:

Part 2:

TOOL 2 – DNA sequencing

It is crucial to know the sequence of subunits in DNA because it is this sequence that forms specific proteins and these proteins carry out specific roles in the cell.

A clever modification of DNA replication makes sequencing possible: modified subunits are used that allow partner binding (A-T and C-G) but doesn’t allow the next subunit in the row to become glued to the modified subunit; thereby stopping replication at this point. For example, imagine the DNA to be read is made up of ATCGATCG. Four separate PCRs are set up with each containing a modified subunit (*) along with all four normal subunits. In the T* reaction replication will be stopped at two places: AT* and ATCGAT*; these can be distinguished by size. Therefore, taken together all four reactions will generate the following bits of DNA:

A* reaction       T* reaction         C* Reaction        G* Reaction


Therefore, the sequence is read left to right as ATCGATCG. This technique formed the basis of the Human Genome Sequencing Project and is therefore one of the most important innovations in human history.

Finding the criminal
Genes within a region are sequenced in sufferers and non-sufferers. For example, gene X in non-sufferers has the sequence TTTATTCCG and in sufferers it is TTTGTTCCG: the fourth subunit A has been replaced by G. This is an A to G mutation (any subunit can be replaced by any other subunit). The criminal has been caught!

Mutations can have a range of affects: stopping the protein from being made, protein is made but it has lost its function, function is subtly altered or the change has no affect. One of the most important ways a mutation has an affect is changing the order of subunits (called amino acids) in proteins. It is the different strings of amino acids that give proteins their specific jobs in the cell.

Wednesday, 29 May 2013

How do Parkinson's researchers discover new knowledge? Part 2

Part 1

TOOL 1 – Polymerase Chain Reaction (PCR)

DNA replication

DNA is made up of two rows of subunits that are joined together to form a double helix shape. Between the rows of subunits A only binds with T and C only with G, so each subunit is facing its partner. The bond between subunits is strong but temporary. DNA replicates itself by breaking the subunit bonds and unzipping its two rows. New subunits bind to its exposed partner and subunits that are next door neighbours are glued together to form rows; thus, one DNA molecule becomes two. DNA replication is controlled by special proteins called DNA polymerases.

An analogy might help to visualise this: imagine a ladder is chopped in half lengthways, resulting in two halves with the rungs of the ladder exposed. Both halves are fixed one rung at a time; thus, one ladder becomes two

Original                        Copies
AATTCCGG               AATTCCGG                      TTAAGGCC
TTAAGGCC               TTAAGGCC         +          AATTGGCC

PCR is the replication of specific bits of DNA and is done in a test tube. All the ingredients (DNA, subunits, DNA polymerase, “primers”) are mixed together at different temperatures; initially DNA is separated into two rows, primers bind to both rows and then DNA polymerase adds each subunit to replicate the original DNA molecule.

The important stage in PCR is binding of the “primers”; primers are very short bits of DNA with a specific subunit sequence (e.g. ATCG and TAGC) designed to bind to a specific region in the DNA to be copied. When two unique primers are used the region of DNA between them will be copied.

             ATCG                                              GCTA                   

The PCR cycle is repeated a number of times to generate lots of copies of the region. In this way repeats can be copied in enough quantity to be seen; DNA of different lengths (e.g. AAAAAAAAAA or AAAA) can be separated by size and visualised by running it through a solid agarose gel.

Once a repeat (or group of repeats) has been found to be present in sufferers the house to house searches can begin in that area; the genes surrounding a repeat are sequenced. A gene is a functional bit of DNA that generates a protein.

Tuesday, 28 May 2013

How do Parkinson's researchers discover new knowledge? Part 1

I will attempt to explain how researchers do their work by describing the tools they use in pursuit of knowledge. These tools include:

  1. Polymerase Chain Reaction (PCR) to generate lots of copies of DNA
  1. DNA sequencing to read the letters of DNA
  1. Expression Plasmids to generate lots of protein from specific genes 
We will see how these tools are used in discovering changes in DNA (i.e. mutations) that cause Parkinson’s.

From the clinic to DNA

A Parkinson’s sufferer is diagnosed and he tells the doctors that some of his relatives also have the disease. This indicates that a mutation causing Parkinson’s might be passed through the generations in this family.

The one thing that is guaranteed to be passed from generation to generation is DNA. DNA is made up of four different subunits (A, T, C, G) and we inherit 3 billion of these subunits. Mutations occur when one subunit is replaced by another. How do we find the one subunit that is mutated in this Parkinson’s family?

DNA mapping

The 3 billion subunits we inherit (collectively called a genome) have distinct landmarks. Imagine you are chasing a criminal and you hear he’s hiding in a house somewhere in London. London has distinctive landmarks and boroughs throughout the city; to find the criminal you split the city into sections and systematically check CCTV and eye witness statements in each section. Lets say there are lots of sightings of the criminal near Big Ben so you narrow your search to houses in that area.

Looking for mutations involves a similar principle but the landmarks in DNA are repeating subunits. For example, at a particular location in the genome there is a repeat that in different individuals will either be AAAAAAAAAA or AAAA. Within the Parkinson’s family sufferers have AAAAAAAAAA while non-sufferers have AAAA. This means that a mutation (e.g. G to T) originally occurred near the repeat in an AAAAAAAAAA individual and both the longer repeat and the mutation causing Parkinson’s are inherited together. Therefore, without knowing the exact location of the criminal we know the area he is in.

But how do we know which repeat is present?

Sunday, 26 May 2013

Don’t let the kettle boil!

My Parkinson’s is like the kettle in the old saying, “a watched kettle never boils”; only I don’t want my Parkinson’s to come to the boil so I watch it intently. However, I don’t know how my Parkinson’s will progress or how long it will take to get to boiling point or whether there is a point at which the whistle on the kettle will sound. In any case, a watched kettle does continue to heat up so obsessively scrutinising every symptom fluctuation without moving on and trying to live some sort of life with the disease is to no propose.

Of course, there are things you can do, ice cubes you can acquire, to cool down the water in the kettle (e.g. medication, cognitive behavioural therapy (CBT), exercise etc). Emotionally, there are insulated gloves you can wear to help you handle the current temperature of your Parkinson’s. Alternatively, you can make the temperature of the kettle feel higher by dragging yourself into an unknown future built on negative expectations.

I can’t do anything about the fact the Parkinson’s kettle has been switched on but I can do something about how to react to the current temperature of the kettle. 

Saturday, 25 May 2013

Losing a sense

I started to notice it when I tasted my food as if through a fog; it was harder to experience, to see, the flavours in my mouth. I then found there was dullness, an absence of sensation, in my nose and I had to reach for the smells I could experience, whereas before smells reached out to me. It seems as if one of the doors through which I access the world is being closed to me; I'm losing my sense of smell. As Kant argues, the means by which we experience the world (e.g. our senses) narrows the totality of the world down to our world; my world has just become narrower still. I'm left with my memory of what things smell like, forever picking at the leftovers of a great banquet.

Of all the things my Parkinson's is doing to me and the strange, baffling, frustrating traffic jams I'm getting caught in, losing my sense of smell is the most unexpected.

Friday, 24 May 2013

Help is a hindrance

One of the most frustrating aspects of Parkinson's is the lack of clarity in the way it presents itself and what I can do about it; each beneficial thing I do has an adverse reaction. For example, medication helps to free up my body but also makes me fall asleep meaning I’m not conscious to benefit from the effect; being active is helpful but it quickly depletes my energy, making it harder to be active next time; taking rests excludes me from others. I long for some stability and a break in the storm so I can work out where I stand…

Parkinson’s is contradictory, unpredictable and constantly shifting.

A portrait of Parkinson’s:

The benefit is a cost

the sun is a cloud

comfort is uncomfortable
eating makes you hungry

a celebration of disappointment                       

                                    the applause is silence,

the page I‘m reading is blank

the music is played silently

pictures on a TV that is turned off

the water is dry

 a black light bulb

the help is a hindrance

Tuesday, 21 May 2013

On Prejudice

Why is the way we look so important to us? Why is something we had no control over and can claim no responsibility for held to be the nucleus of who we are? For example, I was thrown into the world with a particular face and body type but I didn’t choose those characteristics so why am I judged as if I had?

Of course such visual cues are an easy short hand to quickly assess the people we meet but such judgements are entirely arbitrary. Despite the claims of the media there is no “successful” body type or “beautiful” face unless you accept what you are told and believe such a narrow definition. Again, the face you have wasn’t your choice so judgements based on it don’t apply to you; such judgements judge the person making them.

Racist or sexist individuals or those prejudiced against disability make the same error of assuming the judged person is responsible for their skin colour, gender or disability. What nonsense! There is a great difference between possessing a particular thrownness (e.g. I am a white male with Parkinson’s) and being responsible for it (e.g. I didn’t choose to be a white male with Parkinson’s). Such judgements miss the individual being judged and are therefore meaningless.

How should we be judged? For who we are, not what we are.

Monday, 20 May 2013

Broken music

I start to play my instrument but something isn’t right…the instrument is fine, I’m playing it well and the musical score I’m following is perfectly clear. It is something else that has gone wrong: the music itself is broken; in the space between instrument and listener the sound has become scrambled no matter how well I play.

As my mind plays the music of my conscious will, my body no longer listens or dances to the sound. The space between my mind and body, the means of translating mind into bodily action, the reverberating air itself has become corrupted, thick and heavy because of Parkinson’s.

Saturday, 18 May 2013

Fear and Parkinson's

I've just been bundled into a car and the doors have been locked; I'm trapped! The driver, dressed in anonymous black with a black balaclava, has started the car and is speeding down the street. I’m terrified! Tyres screech as we round a corner, going ever faster.

I glance out of the car window and strangely I see myself standing on the street, wearing a lab coat and doing the experiment I was planning before I had to quit my job. Before I can comprehend this image it becomes a blur as we race by. Further along the road I see myself having a romantic meal with a beautiful woman, followed by me wearing a morning suit at a wedding and then pushing a pram; but again we speed past. I look back as these images disappear in the distance.

I scream, "Parkinson's, STOP the car, I want to go back!!!" The car goes ever faster...

Wednesday, 15 May 2013

Parkinson’s medication

The task of life is equivalent to keeping a spinning top turning at the correct speed so it doesn’t fall over; you occasionally have to gently flick it to maintain its momentum and you do this in the plans you make and in your actions.

Parkinson’s makes the spinning top lop-sided so it is more prone to losing momentum and stopping. The flick that would normally work to keep it going isn’t strong enough; your plans and your actions have to succumb to the disease. So, medication is taken to help impart the necessary momentum to keep the spinning top going. However, sometimes the medication has too much of an effect and makes it spin too fast, resulting in unwanted side effects.

I took Levadopa for the first time yesterday; it kept my spinning top turning fairly well and relieved some of my rigidity and slowness of movement. These symptoms feel like I’ve put on clothes three times too small for me; causing the range of possible movement to be curtailed. Medication provides me with baggier clothes to wear. Unfortunately, the Levadopa also gave me overwhelming and irresistible sleepiness.

Keeping that spinning top turning at just the right speed is difficult.

Tuesday, 14 May 2013

Where is meaning located?

Each morning I wake up inside the same head I fell asleep in. Once I’m awake I accompany myself wherever I go during the day. Somehow my awareness is tied to this specific body; even in the midst of other people and different social contexts this link is constant. It follows that the people around us and the society we live in can only temporarily define us; if we rely on these things to give us meaning, we ignore or suppress that which is constant in the different circumstances we encounter: our own self.

Therefore, meaning is located not in the external environment as knowledge moving towards us, but in the opposite direction; meaning is in us as we reach out for the external environment. In other words, meaning is not in the team we support, the religion we believe, the society we live in, the clothes we wear, our peer group, the prognosis of a disease or who we are compared to. Meaning is grounded in our internal self: in how we think, how secure we are in our own skin, why we hold a particular belief and how we relate to ourselves.

Meaning, which is always in relation to a subjective knower, is determined and therefore limited by the state in which the knower exists. This determination is manifest in our ability to choose. For example, Parkinson’s disease is part of the state in which I exist but its meaning is entirely my choice. Seeing the prognosis of Parkinson’s as a rigid future requires me to actively suppress alternative possibilities (e.g. the future is unknown); the meaning of the prognosis as rigid future isn’t imposed externally, it is accepted internally.

Saturday, 11 May 2013

Chronic disease – you are your own doctor (without the training)

It seems to me that as an organisation the NHS misunderstands the nature of Parkinson’s. The NHS is set up for short term intervention following an emergency and it does this well. Within emergency care the Doctor, who has years of training and experience, is dominant and the patient is passive.

A problem arises when this model of care is applied to chronic, incurable, progressive diseases such as Parkinson’s. Within chronic care the patient, who is likely a medical novice, becomes responsible for day to day treatment and the Doctor is relatively passive; the gap between a patient’s medical training and the burden of chronic care is troubling. Shockingly, I was offered no psychological support when I was diagnosed and I was left to the wilderness of the internet (whose content doesn’t have a conscience) to understand what was happening to me. Charities such as Parkinson’s UK do step into the breach but I wonder whether some sort of meeting with Doctors and other health professionals can be arranged a week after diagnosis where patients and their families are taught something of the disease, can ask questions and are set up with some of the tools needed to shoulder the burden of chronic care. Reading a leaflet or a web site, although useful, is a one way conversation.

I am very grateful for the input of my Physio and Occupational therapists (thank you Laura and Mairi!) but it seems I’ve used up my short term intervention tokens because this is gradually stopping. But, Parkinson’s is a shifting disease (new challenges will arise) so the short term intervention model is inappropriate. Also, given the chronic nature of Parkinson’s it will benefit both patient and health professional if a patient could see the same person each time; building trust is crucial in all medical interactions but especially dealing with chronic disease.

Friday, 10 May 2013

Memory and progressive physical disability

There is an important consequence that arises as my movement becomes more challenging: the feeling of my body not working properly becomes set against the memories of what free movement feels like. Therefore, it is not necessarily the impaired movement that causes the emotional damage but the relative gap between expectations based on memories and current levels of movement. Such a gap between feelings makes my current movement appear much worse.

This is the challenge of coming to terms with a progressive disability.

Thursday, 9 May 2013

I don’t care about my symptoms

Before I was diagnosed I was still suffering from the symptoms of Parkinson’s, I just didn’t know it. When the diagnosis came, something changed because life suddenly became a lot harder to deal with. What changed?

I don’t think my symptoms got worse the instant I was told; the act of telling someone they have Parkinson’s doesn’t create or deepen the disease in them. The thing that changed was the awareness of the prognosis of Parkinson’s; it wasn’t the labelling of my symptoms that was important, it was knowledge of how they would get worse in the future. This made my symptoms too important to me in such a way that I obsessively monitored and interpreted each fluctuation in their severity as a prelude to my decline. Soon, my symptoms and the worst possible interpretation of them was all I could see. I cared too much about the prognosis until it became hyper-real and certain.

Prognosis means predicting the likely outcome of a disease. Can we ever know the future? The prognosis of Parkinson’s allowed me to build an elaborate and detailed future that was made out of nothing, merely thin prediction and likelihood. I became lost in this empty “future” and as a result missed my present circumstances as a whole. To escape the prison of a non-existent “future” you have to break it at the source; you have to declare, I don’t care about my symptoms. Try to recapture the feeling pre-diagnosis of the symptoms lived in day by day, naked without the empty finery of a prognosis.

A diagnosis of Parkinson’s is very difficult emotionally because it stretches you into a non-existent future. Due to its non-existence, you are powerless to change this “future”. Seeing the symptoms in the context of now, which means caring a little less about them, ensures you remain in the present. 

Tuesday, 7 May 2013

Solve the jigsaw puzzle and you can move!

My body is like a giant jigsaw puzzle with my limbs, organs and other body parts all jumbled up. When I want to move I must painstakingly rearrange the pieces into their correct position; this laborious mental effort completes the circuit between my mind and my body. Once this happens something releases in my body and I can move, like a dog straining at the leach that is suddenly given his freedom.

As I'm moving I can feel myself unraveling and becoming jumbled up again until the circuit is broken. Then I have to start the whole process again. As my symptoms have worsened the jigsaw pieces have become smaller, requiring more time to set in place. It is mentally and physically exhausting. 

The dangers of “normal”

Society projects an idea of what is “normal”; we reach for this ideal and in the process become predictable. The meaning of the ideal of “normal” is to ensure we engage with and contribute to that particular society’s survival. As part of this projection, we are assaulted on a daily basis by the empty images of advertising and feel the pressure to conform to the society we find ourselves in. In the process we are compelled to compare ourselves to others. In the case of advertisers, the “normal” life they project is deliberately unobtainable so we buy the product to make up for the perceived inadequacy in our own lives; somehow having the product makes us “normal”. Of course, the life they project is nonsense and the fulfilment of owning the product is short lived as fashion and the definition of “normal” moves on.

This is in direct conflict with the individual, varied and unique lives we lead. Therefore, any comparison with what is “normal” is comparing like with unlike and inevitably results in disappointment with yourself; this implicit inadequacy and disappointment is the nourishment of all religions and companies.

This is a particular problem for those who fall shorter of “normal” and are deemed disabled. For example, Parkinson’s sufferers can be drawn into comparing themselves to other people (and also to their past selves) and feel the loss imposed by the disease.

However, all notions of what is “normal” are relative and partial. We are free to choose our own “normality” and who we compare ourselves to. Of course, taking on this freedom shackles us with responsibility for the choices we make. Many of us follow, without question, society’s “normality” to avoid such a burden.

Saturday, 4 May 2013

On Impairment and Disability

1. Impairment

I define “impairment” as the underlying disease process that impacts a person (e.g. in Parkinson’s disease it is loss of nerve cells in the brain). The identification of a particular aberrant function of the body and attempts to eliminate or manage the disease process is the responsibility of the medical profession.

Impairment is part of what Heidegger calls the “thrownness” of the impaired person; in other words, part of the state in which that person exists, as determined by events before her birth (or before she was “thrown into the world”). Agency, defined as self-determination, arises only after we are born. It follows that thrownness, which is set up before birth, is not self-determined: meaning that the impaired person is not responsible for the impairment or indeed any aspect of thrownness. It is true, the person possesses the impairment but she is not the agent responsible for the possession (there is no agent responsible for thrownness, it just is).

Criticism of the medical profession for “pathologising” the impaired person is misplaced for two reasons; firstly, it is a form of self-denial to believe the impairment is not present; second, the pathology describes a small part of thrownness and since the impaired person isn’t responsible for their thrownness the pathologising misses the whole person and just hits upon the impairment.

2. Disability

The concept of “disability” arises from comparing the impaired person to those whom are different to her. An example will demonstrate this: we all have an impairment in that we can only see in the visual part of the light spectrum. But this isn’t called a disability because no one can see the rest of the spectrum; disability is a relative term, it needs others with a comparative ability to have any meaning.

The impairment is important here only as a means of differentiating the impaired person from those around her. But, we were all thrown into the world with varying abilities and impairments and therefore, depending on whom we are compared to, we can all be defined as disabled. Disability is a fragile and muddled concept.

The notion that disability is made by the inaccessibility of the environment is predicated on a false expectation of similarity among all people (i.e. ignoring the presence of the impairment). Environmental disability has nothing to do with the impaired person; it is due to the assumed ability of the “average” person that the urban planners catered for. It is gratifying to see during the past 30 years the definition of “average” has broadened to include varying abilities, resulting in a more open environment. However, there is no environment that can eliminate the presence of the impairment, it can only lessen its impact.

3. Conclusion

“Ability”, “disability”, “average person” are all relative terms and cannot be absolutely defined. In contrast, the “impairment” is either present or absent. Therefore, I see disability as a weaker concept in that it relies on the (usually negative) comparison with other people and misses the impact of the impairment on the impaired person. I believe it is crucial, as far as possible, to empower the affected person with knowledge, tools, adaptations, financial support and psychological help to enable, despite the impairment, a free exercise of their agency. Those of us with greater difficulty in expressing our agency should receive more help. Such social care must be for some purpose, an enabling of agency, and not an end in itself; for example, a person is helped to shower and dress in the morning but left all day to stare at a blank wall; the care has led to nothing and therefore has lesser value.

Friday, 3 May 2013


Imagine you are out shopping and you come across two shops next door to each other. One is brightly lit, the front door is open and the windows of the shop are large and allow you to see the entire interior of the shop. In contrast, the other shop has no lights on inside, the windows are small and made of frosted glass and the door is closed. Which shop would you go into?

Being open about my Parkinson’s enables me to engage with it in a more proactive way; I’m not hesitating outside the second shop, I’m browsing inside the first shop understanding and choosing the best options for me.

All people and organisations associated with Parkinson’s (Doctors, Parkinson’s Nurses, Parkinson’s UK, Researchers, Physiotherapists, Occupational therapists, sufferers and their family and friends) should set up their various shops on the Parkinson’s high street to be accessible and transparent; this empowers themselves (more people will visit their shop) and also empowers sufferers to cope, day to day, with their disease.

Thursday, 2 May 2013


We had been sailing on the oceans for years, looking for land and somewhere to build a new home. The ship was crowded with passengers and crew hoping for a new start. Then it happened; a thin line of green appeared on the horizon, “Land ahoy!” and everyone rushed to see. We sailed closer and the green line resolved into a vast coastline. All on board cheered with joy and relief!

It was decided to send a small group ashore to set up a camp; I was one of these initial settlers. The land was strange, but full of delicious and abundant fruit and after years on board ship we gorged ourselves. Then we made a clearing in the forest and set up camp. On the second day we met the native people of this land; strangely, they ignored us as if we had never arrived.

Over the next few years we vastly expanded the camp, cutting down more of the forest for housing and fuel, and rapidly moved inland. As we claimed the land as our own we displaced the natives from their homes and devoured the natural resources.

We had established a firm foothold and a thriving community before the natives reacted; but, by then, it was too late, our invasion was inevitable.

And, to think, all this came from one ship; the name of that ship…Parkinson’s.

Wednesday, 1 May 2013

"Ain't it a life?"

My life is a juxtaposition and a contradiction. At one moment I'm accepting of my situation and the next I'm embroiled in frustration. I refuse to inhabit the role of a Parkinson's sufferer and then lose myself in the disease. I never take things for granted but I mourn the passing of the time when I did. My expectations and my future struggle to come to terms with what’s happening to me now; everyday tasks take up more of my capacity, leaving undone love and happiness and acquainting me with fear and onlyness.

My initial blissful ignorance slowly gave way to understanding the Parkinson's role that was thrust upon me at diagnosis. Awareness can be a curse. I’ve tried to climb the learning curve, slipped many times but managed to keep on going. It is an uneven journey, which best reflects the nature of the disease; Parkinson's is constantly changing and I'm always trying to catch up.

In mundane everyday life, there is dignity in the struggle with undignified Parkinson's; bravery in being honest about my disease; courage in taking another step; real achievement in learning to live alongside Parkinson’s disease. But to what purpose? To help others with my example? Maybe struggle has no meaning except learning to struggle in a better way.

Is this a life? It is my life.