it,’ he said.
With what Weinberg calls ‘irrational enthusiasm – totally irrational and illogical’, Friend went ahead. He struck up a collaboration with a doctor working at the nearby
Massachusetts Eye and Ear Infirmary, Ted Dryja, whose caseload at the hospital included children with retinoblastoma. Driven by concern for his small patients as well as by intellectual curiosity
and the desire to learn something about DNA, Dryja, who had no formal training in molecular biology, had started to do some lab research to try to find out what lay at the root of this dreadful
affliction. Focusing on chromosome 13, he had chopped out and cloned small fragments of the DNA. For him, this was just a means of acquiring some basic skills, but these clones created useful
probes for investigating the chromosome further. Dryja shared his new tools with Steve Friend and, soon after the young scientist began his search, ‘Lo and behold, one of these probes landed
right in the middle of the retinoblastoma gene and allowed it to be cloned out,’ Weinberg told his audience in the lecture hall at MIT. Spreading his arms wide to emphasise the length of the
DNA strand, then stabbing with his finger to indicate the extraordinary landing site of the probe, right on target, Weinberg spoke with a voice slow and deliberate with amazement. ‘Now you
know how many mega-bases each human chromosome is long; and you know how astronomically unlikely this stroke of luck was – or is. But it happened . . . This is what’s termed an
“unearned run”. It was a terrific finding.’
Steve Friend and Ted Dryja published their story in
Nature
in October 1986 and now the world was listening. A scientist called Webster Cavanee, then a postdoc at the University of Utah,
had earlier narrowed the field of search down even further, to a specific region on chromosome 13, and his 1983 paper was the first to confirm that Knudson’s two-hit hypothesis was right. On
hearing the news that the actual gene had been found and cloned, Cavenee commented, ‘I take my hat off to these guys. You can call it luck, but they did the right experiment, an elegant
experiment, and it worked. What more do you have to do before they stop calling you lucky and start calling you a good scientist?’
Alfred Knudson, too, was excited. ‘I’m delighted this has happened,’ he said. ‘Before, we could only concoct theories about what the retinoblastoma gene does. Now that we
have the gene, we can get to work on the facts.’
This was nothing less than a paradigm shift – a whole new way of looking at tumour formation as a battle of competing forces between oncogenes and tumour suppressors, the accelerators and
brakes of our car analogy above. It led also to the recognition, finally, that cancer is altogether an aberration. Oncogenes are not there primarily to drive cancer, and tumour suppressors are not
there primarily to suppress cancer; all these genes have regular work to do, including promoting or controlling the growth of cells as part of the endless cycle of building and maintaining our
bodies. Only when these vital genes become corrupted and start to malfunction do they acquire the ability to cause cancer.
When, very soon afterwards, p53 was finally revealed as being the same kind of gene as the retinoblastoma gene – a tumour suppressor, and a powerful one at that – it had an
electrifying effect on the field. Researchers reacted like a flock of starlings over a winter field, wheeling around to fly in a new direction, and those who had begun to lose faith in p53 and to
consider moving on to other things returned to their work with renewed enthusiasm.
CHAPTER EIGHT
p53 Reveals its True Colours
In which we hear of the brilliant work and strokes of luck that showed normal p53 to be a tumour suppressor not an oncogene – its job being to press on the brake
rather than the accelerator pedal in cells with damaged DNA.
***
People don’t realise that
With what Weinberg calls ‘irrational enthusiasm – totally irrational and illogical’, Friend went ahead. He struck up a collaboration with a doctor working at the nearby
Massachusetts Eye and Ear Infirmary, Ted Dryja, whose caseload at the hospital included children with retinoblastoma. Driven by concern for his small patients as well as by intellectual curiosity
and the desire to learn something about DNA, Dryja, who had no formal training in molecular biology, had started to do some lab research to try to find out what lay at the root of this dreadful
affliction. Focusing on chromosome 13, he had chopped out and cloned small fragments of the DNA. For him, this was just a means of acquiring some basic skills, but these clones created useful
probes for investigating the chromosome further. Dryja shared his new tools with Steve Friend and, soon after the young scientist began his search, ‘Lo and behold, one of these probes landed
right in the middle of the retinoblastoma gene and allowed it to be cloned out,’ Weinberg told his audience in the lecture hall at MIT. Spreading his arms wide to emphasise the length of the
DNA strand, then stabbing with his finger to indicate the extraordinary landing site of the probe, right on target, Weinberg spoke with a voice slow and deliberate with amazement. ‘Now you
know how many mega-bases each human chromosome is long; and you know how astronomically unlikely this stroke of luck was – or is. But it happened . . . This is what’s termed an
“unearned run”. It was a terrific finding.’
Steve Friend and Ted Dryja published their story in
Nature
in October 1986 and now the world was listening. A scientist called Webster Cavanee, then a postdoc at the University of Utah,
had earlier narrowed the field of search down even further, to a specific region on chromosome 13, and his 1983 paper was the first to confirm that Knudson’s two-hit hypothesis was right. On
hearing the news that the actual gene had been found and cloned, Cavenee commented, ‘I take my hat off to these guys. You can call it luck, but they did the right experiment, an elegant
experiment, and it worked. What more do you have to do before they stop calling you lucky and start calling you a good scientist?’
Alfred Knudson, too, was excited. ‘I’m delighted this has happened,’ he said. ‘Before, we could only concoct theories about what the retinoblastoma gene does. Now that we
have the gene, we can get to work on the facts.’
This was nothing less than a paradigm shift – a whole new way of looking at tumour formation as a battle of competing forces between oncogenes and tumour suppressors, the accelerators and
brakes of our car analogy above. It led also to the recognition, finally, that cancer is altogether an aberration. Oncogenes are not there primarily to drive cancer, and tumour suppressors are not
there primarily to suppress cancer; all these genes have regular work to do, including promoting or controlling the growth of cells as part of the endless cycle of building and maintaining our
bodies. Only when these vital genes become corrupted and start to malfunction do they acquire the ability to cause cancer.
When, very soon afterwards, p53 was finally revealed as being the same kind of gene as the retinoblastoma gene – a tumour suppressor, and a powerful one at that – it had an
electrifying effect on the field. Researchers reacted like a flock of starlings over a winter field, wheeling around to fly in a new direction, and those who had begun to lose faith in p53 and to
consider moving on to other things returned to their work with renewed enthusiasm.
CHAPTER EIGHT
p53 Reveals its True Colours
In which we hear of the brilliant work and strokes of luck that showed normal p53 to be a tumour suppressor not an oncogene – its job being to press on the brake
rather than the accelerator pedal in cells with damaged DNA.
***
People don’t realise that
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