Germline therapy tipped for longer life

Evolution doesn't care what happens to the body after reproduction, says Prof Miroslav Radman, so we humans should consider taking out little extra cellular life insurance to ward off cancer in our twilight years.

Radman, a world-renowned expert in cellular DNA-repair systems at the Necker Medical School at the University of Paris, suggests that humans should consider germ-line gene therapy to install two extra copies of the P53 tumour-suppressor gene -- popularly known the 'the guardian of the genome'.

Radman's team has already created a transgenic mouse strain backup P53 genes. "In these mice with three of four P53 genes, cancer is much reduced and the life quality of aging appears normal," he said.

"Are you ready to start having forbidden thoughts? We have created a superior mouse, and we say, 'You should be happy because we have changed your germline and your children will profit from that.

"Could we start thinking of human germline modification -- could it be a genuine scientific project [whose benefits] would last for millennia?"

Radman described how the loss or suppression of cellular DNA-repair systems spawns fast-mutating strains of bacteria that have developed resistance to most modern antibiotics, and cancerous cells that can become resistant to chemotherapy.

He says the aim should be to prevent cancer, rather than treat established cancers, and P53 is potentially the best insurance available.

P53 monitors dividing cells for dangerous mutation loads, and instructs potentially cancerous cells to commit 'suicide' -- apoptosis. But P53 itself is as susceptible to mutation as any other human gene. Radman says the loss of one copy of the gene in a cell is dangerous, but the loss of both copies is catastrophic.

The loss of the second copy of P53 is commonly the "last straw" event that tips a mutation-ridden cell into runaway growth and division -- geneticists have found that P53 is inactivated by mutation in more than 60 per cent of cancers.

Somewhere among the world's 6 billion human beings, says Radman, there are probably a few individuals who have acquired an extra copy of P53 through gene-duplication events -- they unknowingly enjoy extra protection against cancer.

Identifying them would be difficult, but Radman joked that he would like to introduce his niece to "Mr Super P53".