The Koyal Group Info Mag Review P53: The Gene That Cracked

the Cancer Code by Sue Armstrong review

A cure for cancer the phrase is so often repeated, surely it must finally
materialise? To anyone not familiar with the developing story of cancer research, the
position seems tragically unsatisfactory. Billions of pounds and decades of work by
thousands of researchers have produced much better prognoses for some cancers, but
harsh forms of chemotherapy and radiotherapy are still the standard treatment and the
much sought-after magic cure remains tantalisingly out of reach.

As Sue Armstrong points out at the beginning of her book, while we may naively
wonder why so many people get cancer, researchers are asking Why so few?. Every
time a cell divides skin and digestive-tract cells are constantly proliferating there is
a possibility of genetic errors. For cancer to develop, it requires the control mechanism
in just one cell to be thrown into disorder, resulting in unlimited replication of that
rogue cell. Considering the stupendous number of cell divisions occurring in the human
body the development of cancer is rare. Scientists have long suspected that there is a
very powerful protective mechanism at work.

P53 (the name refers to a protein of

molecular weight 53 kilodaltons) is the
cancer prophylactic for most multicellular
organisms; it has been dubbed the
guardian of the genome. While cancer has
many causes and can be insidiously
malignant throughout the body, p53 is the
single most unifying factor in the disease:
for most kinds of cancer to develop, p53s

suppressor activity has to have been disabled.

It has taken scientists a long time to establish some of the basic facts about cancer. In
1911 the pathologist Peyton Rous reported a virus that caused cancer in chickens. For
decades this finding was dismissed: cancer, according to the official line, could not be
caused by a virus. Rous lived long enough to see Francis Crick and James Watsons
double helix structure of 1953 establish DNAs role at the heart of life and for his own
theory to be subsequently vindicated; he received the Nobel prize in 1966 for his
pioneering work.

How did we come to probe these minute molecular workings of nature? Most popular
texts on genomics and molecular biology blithely report the results without offering any
insight into how the scientists have reached their conclusions. Armstrongs book has
one of the best accounts Ive read of how science is actually performed. She asks, what
can they actually see? When it comes to a gene, which is only two nanometres wide, the
answer is nothing; they work by inferring from experiments on things that they can
see. As she says: It is the unseeable nature of molecular biology that makes it so
difficult to grasp. She quotes one of her scientists, Peter Hall: its based on faith,
ultimately. And even when scientists have a good sense of what their experiments are
telling them, theyre up against the fact that life is an immensely complicated process:
we can land a probe on a distant comet after a 10-year flight because the Newtonian
clockwork of bodies in space is predictable. But all-embracing laws of biology are hard
to find.

The process of discovery goes like this (and p53 is a classic example): something
unexpected and odd turns up; investigation begins; its character gradually becomes
clearer but its purpose remains a mystery; then evidence accumulates to suggest a
function. That evidence is often misleading and, in the case of p53, a function
diametrically opposed to the true one was ascribed to it for 10 years: it was thought to
be a cancer-causing protein. Then came the moment of clarity and the potentially great
unifying principle was born: in 1989, P53 was revealed as the master tumour
suppressor an order was established at last.

There are great hopes that our knowledge of p53 will lead to novel cancer treatments,
but the pattern has grown much more complicated since then. In some situations p53

can cause cancer. For cancers to grow they need a mutated and disabled p53: in
science, these cycles of discovery go on forever, and so will the battle between cancer
and p53.

But progress is being made. One of the brightest hopes for therapy using p53 is in
families with a predisposition to cancer. The reason for this blight is that the family
members have each inherited a mutant copy of p53 and are therefore without the
normal protection it provides. An experimental gene therapy (Advexin) already exists
to correct this, but in 2008 the US regulatory body refused to license the treatment. A
similar product, Gendicine, is licensed in China and approval for its clinical use is being
sought in the US. One common story in todays medical research is of remarkable
possibilities constantly being blocked by a sluggish regulatory system and the skewed
priorities of Big Pharma, which prefers to develop bestselling drugs that will have the
widest use.

Armstrongs book will offer many readers a sense of hope, but might also induce
intense frustration at the long time it takes for discoveries in the lab to filter down to
hospitals and the marketplace. Nevertheless, we can be sure that p53, even if it is not
the cure for cancer, will have an honourable role to play in our attempts to find one.

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