When Stephen Hawking was diagnosed with amyotrophic lateral sclerosis (ALS) in 1963, few thought he would live more than a couple of years.
At the time he was diagnosed, Professor Hawking asked a question often posed when people are diagnosed with a terminal illness — why me?
He wrote about this in his memoir, My Brief History.
"I felt it was very unfair — why should this happen to me?
"At the time, I thought my life was over and that I would never realise the potential I felt I had."
But Professor Hawking lived decades longer than he, or many medical experts, expected that he would.
How Hawking's disease progressed
Professor Hawking had just turned 21 when he was diagnosed with a very rare slow-progressing form of ALS, a form of motor neurone disease (MND).
He was at the end of his time at Oxford when he started to notice early signs of his disease. He was getting more clumsy and fell over several times without knowing why.
In comments published in a 2002 British Medical Journal article close to his 60th birthday, Professor Hawking recalled going to hospital for medical tests.
"I was in for two weeks, during which I had a wide variety of tests. After all that, they didn't tell me what I had, except that it was not multiple sclerosis, and that I was an atypical case.
"I gathered, however, that they expected it to continue to get worse, and that there was nothing they could do, except give me vitamins.
"I could see that they didn't expect them to have much effect. I didn't feel like asking for more details, because they were obviously bad.
"The realisation that I had an incurable disease that was likely to kill me in a few years was a bit of a shock."
The details Professor Hawking didn't want to ask for are very grim.
The average life expectancy of someone with MND is between two and three years, most people die within five. Professor Hawking lived for more than five decades after he was diagnosed.
But his health was affected significantly within a few years of his diagnosis.
By the late 1960s, he was using a wheelchair to move around and was having trouble writing.
His speech began to deteriorate in the 1970s.
In 1985 he became ill with pneumonia on a trip to CERN in Geneva. To help him breathe again, doctors did a tracheotomy, which meant they had to cut a hole in his neck and place a tube into his windpipe. Professor Hawking irreversibly lost the ability to speak.
From then on he spoke through his computer system — which he operated with his cheek — and had to have around-the-clock care.
Loading...How did he survive for so long?
Every time Professor Hawking passed a milestone, medical experts speculated as to why he survived for so much longer than most people with ALS.
In the BMJ article, Professor Nigel Leigh of King's College, London, said he was "not aware of who has survived with MND as long. What is unusual is not only the length of time, but that the disease seems to have almost burnt out".
Professor Leigh suggested those who develop the condition when they were younger tended to survive longer, sometimes for as long as 10 years.
"Among people in their 50s and 60s, there is a 50 per cent chance of surviving four years or so. It is a different beast if you start young, oddly, and no one knows why.
"But even some forms of MND that start in the [patient's] 50s or 60s can be slowly progressive."
In 2012, when Professor Hawking reached 70, Scientific American interviewed Associate Professor Leo McCluskey from the ALS Centre at the University of Pennsylvania.
He also made the point that the early onset of Professor Hawking's disease was likely part of the reason why it had progressed so slowly.
But he also suggested that Professor Hawking's survival was likely due to a combination of the care he received and the biology of his illness.
"If he really isn't on a ventilator, then it's his biology—it's the biology of his form of the neurodegenerative disease that determines how long he will live.
"For trouble swallowing, you can elect to have a feeding tube placed, which basically takes malnutrition and dehydration off the table.
"But mostly it's about the biology of the disease."
Professor Hawking said he believed the disease had many different causes and that his may be have been due to the poor absorption of vitamins.
Loading...What is ALS?
Also referred to as Lou Gehrig's disease, ALS is the most common type of MND, involving the degeneration and eventual loss of the nerves that relay signals to the muscles.
(To clarify, MND is the widely used generic term in Australia, the UK and parts of Europe. ALS is used more generically in the United States, Canada and South America.)
The damage can happen in the brain, the spinal cord or peripheral nerves, which connect the brain and spinal cord to the rest of the body.
It causes involuntary muscle contraction, also known as spasticity, alongside weakness and muscle wasting.
The disease affects men and women equally. It usually begins in mid- to late adult life and gets more common with age, although more people appear to be developing MND in early adult life.
We don't know what causes the majority of cases of motor neurone disease.
About 5 or 10 per cent of cases are inherited, and the genetic link of about 60 per cent of these cases is now known in Australian families.
As the condition progresses, the symptoms get worse, more areas become involved and function is progressively lost.
Eventually paralysis strikes the muscles of the throat, diaphragm and chest, causing difficulties swallowing and breathing.
The senses of eyesight, hearing, taste, smell and touch aren't affected, and nor is bladder and bowel function.
Distressingly, the patient remains fully conscious and aware as they become progressively paralysed.
Death is usually caused by respiratory failure or pneumonia.