After being diagnosed with a rare form of motor neurone disease in 1964 at the age of 22, Stephen Hawking was given just a few years to live.
Nearly half a century later, he is celebrating his 70th birthday as one of the most brilliant and celebrated scientists of the modern age.
Despite his illness leaving him almost completely paralysed and unable to speak, Prof Hawking's countless scientific papers, best-selling books and numerous awards have earned him comparisons with Albert Einstein and Sir Isaac Newton.
But with his distinctive computerised voice, Prof Hawking is as much a celebrity as he is a scientist, appearing on TV cartoon The Simpsons, starring in Star Trek and providing narration for a British Telecom commercial that was later sampled on a Pink Floyd album.
Born in Oxford on January 8 1942 - 300 years after the death of astronomer Galileo Galilei - Prof Hawking grew up in St Albans.
He had a difficult time at the local public school and was persecuted as a "swot" who was more interested in jazz, classical music and debating than sport and pop.
Although not top of the class, he was good at maths and "chaotically enthusiastic in chemistry".
As an undergraduate at Oxford, the young Hawking was so good at physics that he got through with little effort.
He later calculated that his work there "amounted to an average of just an hour a day" and commented: "I'm not proud of this lack of work, I'm just describing my attitude at the time, which I shared with most of my fellow students.
"You were supposed to be brilliant without effort, or to accept your limitations and get a fourth-pclass degree."
Hawking got a first and went to Cambridge to begin work on his PhD, but already he was beginning to experience the first symptoms of his illness.
During his last year at Oxford he became clumsy, and twice fell over for no apparent reason. Shortly after his 21st birthday he went for tests, and at 22 he was diagnosed with amyotrophic lateral sclerosis (ALS), a form of motor neurone disease.
The news came as an enormous shock that for a time plunged the budding academic into deep despair. But he was rescued by an old friend, Jane Wilde, who went on to become his first wife, giving him a family with three children.
After a painful period coming to terms with his condition, Prof Hawking threw himself into his work.
At one Royal Society meeting, the still-unknown Hawking interrupted a lecture by renowned astrophysicist Sir Fred Hoyle, then at the pinnacle of his career, to inform him that he had made a mistake.
An irritated Sir Fred asked how Hawking presumed to know that his calculations were wrong. Hawking replied: "Because I've worked them out in my head."
In the 1970s Hawking, already confined to a wheelchair, produced a stream of first class research, including probably his most important contribution to cosmology.
This was the discovery of Hawking radiation, which allows a black hole to leak energy and gradually fade away to nothing.
By applying quantum mechanics to black holes, he had taken the first steps to combining quantum theory and general relativity.
One describes the universe at the sub-atomic level, and the other at very large scales. Bringing the two theories together is one of the great unfulfilled goals of modern physics.
In the 1980s, Prof Hawking and Professor Jim Hartle, from the University of California at Santa Barbara, proposed a model of the universe which had no boundaries in space or time.
The concept was described in A Brief History Of Time, which sold 25 million copies worldwide.
Upheaval in his personal life, as well as scientific achievements, has cemented Prof Hawking's place in the public eye.
In February 1990 he left his wife of 25 years to set up home with one of his nurses, Elaine Mason. The couple married in September 1995 but divorced in 2006.
Prof Hawking has been showered with honorary degrees, medals, awards and prizes throughout his career, and in 1982 was made a CBE.
At times, he has also ruffled the feathers of the scientific establishment with far-fetched statements about the existence of extraterrestrials, time travel, and the creation of humans through genetic engineering.
He has also predicted the end of humanity - due to global warming, a new killer virus, or the impact of a large comet.
Perhaps this unorthodoxy is one reason why the greatest accolade of all, the Nobel Prize for Physics, continues to elude him.
In recent years, Prof Hawking has examined the relationship between science and religion, writing a 2010 book Grand Design, which argues that evoking God is not necessary to explain the origins of the universe. He met the Pope at a scientific event hosted by the Pontifical Academy of Sciences in 2008.
As he enters his 71st year, Prof Hawking's illness continues to take its toll. Reports have suggested he may face losing his famous computerised voice because his cheek muscles which power the technology behind it are deteriorating.