A few days after he was paralysed from the neck down in a riding accident in 1995, Superman actor Christopher Reeve told his wife, Dana: "Perhaps we should let me go."
His despair was understandable, but it proved short-lived: within months, Reeve, who died at the weekend aged 52, had become a passionate campaigner for medical research, driven by a combination of optimism and anger that led both to controversy and unprecedented scientific advances.
Joining the tributes yesterday, the Democratic presidential candidate, John Kerry, said Reeve had been "truly America's hero" for his advocacy of stem cell research.
The actor suffered a heart attack and fell into a coma at his home in Pound Ridge, near Bedford, New York, on Saturday after developing a systemic infection from a pressure wound. He died in hospital the next day, surrounded by his family.
His support for stem cell research had turned a controversial issue into a mainstream matter, keeping it high on the political agenda in the US even in the last days of his life.
Wise Young, who treated Reeve after his accident, yesterday told the Guardian he was "heartbroken", and applauded his patient's legacy. "He's been given a lot of credit for raising money and publicity, but one thing that isn't said a lot is how much he motivated scientists. He raised the ambition of the research enterprise by using the word 'cure', as opposed to 'rehabilitation' or 'restoring some function' ... When he asked me a few weeks after his injury whether there was any therapy that could help, and I said yes, he immediately asked how long, and I said seven years. He said: 'Well, let's make that a goal.' So he went to the media and told them: 'If we fail, we tried.' I think that was his attitude."
But while Reeve sought to be "realistically optimistic", he never hid the realities of his condition. "It bothers me when people say, 'You played Superman, now you are Superman'," he once observed.
"They mean well, but they don't know what I go through in the middle of the night."
Yesterday Dana thanked his personal staff of nurses and aides "as well as the millions of fans from around the world who have supported and loved my husband over the years".
The actor's wealth, celebrity and determination ensured that he received the best and most advanced care.
But pressure sores are one of the biggest health fears of people with spinal injuries. They develop because areas of the skin, such as the buttocks and the backs of the legs and ankles, are in almost permanent contact with beds or chairs.
The pressure reduces the blood supply to the skin and causes the tissue underneath to atrophy. Without attention, the damage can spread to the muscle and as far as the bone. If it reaches the bloodstream, it can prove lethal.
In Reeve's case, the treatment, which involved administering intravenous antibiotics to his already weakened body, triggered a cardiac arrest.
"Christopher's condition was one that was fairly frail and susceptible to problems and his body had taken a bit of of an onslaught. When you have an infection like that it really does take it out of you," said Paul Smith, executive director of the Spinal Injuries Association, which Reeve supported.
He said the actor had brought attention and funding to an often ignored condition. "He also showed you can live your life and that it isn't the end of everything important. He believed we needed to look to the future, but also to support people here and now."
Lord May of Oxford, the president of the Royal Society, said: "His invaluable contribution has raised awareness of this issue in a way that no one within the medical or scientific communities could ever have hoped to achieve."
Last night, President Bush issued a statement saying he and his wife, Laura, were saddened by Reeve's death and sent prayers and condolences to his family and friends.
"He will be remembered as an accomplished actor and for his dedicated advocacy for those with physical disabilities," he said.
The actor and comedian Robin Williams said: "The world has lost a tremendous activist and artist, and an inspiration for people worldwide. I have lost a great friend." The film director Michael Winner described Reeve as the "archetypal movie star" and a man of great charisma, while Susannah York, who starred with him in Superman, praised his generosity of spirit.
Reeve was a virtual unknown when he was picked from 200 hopefuls to star in Superman. The film and its sequels grossed $300m (£167m), but Reeve sought to "escape the cape" in later screen and stage work.
After his accident, he successfully lobbied Congress for better insurance protection against catastrophic injury, became chairman of the American Paralysis Association and created his own foundation to raise money for research and support those with disabilities. He also revived his professional career, directing films and winning a Screen Actors Guild award for his role in a remake of the Hitchcock thriller Rear Window.
By 2002 Reeve had regained sensation in much of his body and could move some of his fingers and toes. Doctors described the progress as remarkable given the severity of his injuries. He could also breathe for longer periods without a respirator. Hopes that he would be walking by his 50th birthday, however, proved baseless .
Speaking to the Guardian that year, he said: "I find that it's best to think, well, what can I do today? Is there something I can accomplish, a phone call I can make, a letter I can write, a person I can talk to, that will move things forward?"
In a recent interview with Reader's Digest, to be published this year, the actor said he had become more patient. But he added: "I also know that, with time, I'm beginning to fight issues of ageing as well as long-term paralysis."
Reeve appeared to be coming to terms with the idea that big improvements in his health were unlikely.
In a documentary filmed in May and due to be shown on the BBC next week, he described suffering setbacks and said his recovery had plateaued. "I'm in very good health, but it hasn't turned into an improvement in function that would really change my life." But he added: "I feel very confident that I'm strong enough ... that I'll be prepared for whatever medical intervention comes my way."
In the same film, Dana said that last winter was "very, very tough".
"Pretty much December was all about the hospital and trying to get better," she said. "And at the hospital he got some more sacral wounds, which are very hard to get rid of, pressure sores, skin breakdown, and it can completely alter your quality of life, and it did for him."
