Free p53 by Sue Armstrong Page A

is
     what almost everyone – erroneously – concluded p53 to be.
    ***
    Scientists, like anyone confronting a new problem, will start with what they already know. Neither in theoretical speculation nor at the bench do they often sail
     beyond sight of the shore.
    Horace Freeland Judson
    As they set about their investigations into how p53 functions, thoughts of oncogenes were uppermost in many researchers’ minds, since the first such gene in human DNA had
been discovered just months earlier, in 1982. Once again Bob Weinberg, one of the pioneers of oncogene research, was there at the cutting edge, and here we need to retrace our steps a little to see
how the oncogene story developed.
    Weinberg was born in Pittsburgh, Pennsylvania, and raised in the United States by a mother, father and grandparents who had arrived as refugees from Europe in the late 1930s. His father, a
dentist in Germany, had seen the writing on the wall as the Nazi threat grew and had been smuggling money out of the country to a brother in the Netherlands. When he finally fled to the US in 1938,
he had enough money saved to retrain and re-certify as a dentist in his new home. Though the younger Weinberg had no direct experience of Fascism, the suffering of his family in Europe, where many
of them did not escape or survive the Holocaust, percolated into his consciousness and he grew up with a keen sense of the precariousness of life. ‘One thing my father said to me was,
“It’s okay to be successful and productive, but don’t be too visible lest the guys in the brown shirts come in one night and take you away.”’
    Although this man with the bushy moustache, self-deprecating humour and Woody Allen-ish face insists he’s happiest in mud-caked overalls, pottering in his garden or splitting logs, he is
undoubtedly the most visible of a bunch of scientists in three different labs who all made the momentous discovery of the first human oncogene at the same time. 5 Undeterred by the scandal caused by the fraudulent Canadian research described in Chapter 2 , he and his team continued to investigate the phenomenon they had discovered and
reported in 1979 – that rodent cells contain would-be oncogenes that can be activated by chemical carcinogens as well as by infection with viruses. By 1981 his lab, with that of Geoffrey
Cooper at Harvard Medical School in hot competition, had shown that oncogenes are to be found in human tumour cells too.
    Both labs had used the same ingenious and relatively new technique called ‘transfection’ in their research. This involves taking pure DNA from tumour cells, chopping it up and
putting it in solution with normal cells that are the researcher’s target. By tinkering with the solution, the scientist can induce the cells to take up some of the pure DNA floating around
and to integrate it into their own genomes. He or she then cultures the cells in Petri dishes and looks for evidence that they have turned cancerous. The cells in our bodies talk to each other
constantly: normal cells obey instructions that ensure orderly growth and usually stop them dividing once they have formed a single layer in the Petri dish and filled the available surface space.
Cancerous cells, however, are unruly: they talk anarchy, pile on top of one another and form haphazard clumps, known as foci, in the dishes. Thus Weinberg’s and Cooper’s teams looked
for foci – and found them.
    Homing in on the specific gene or genes responsible was an infinitely painstaking process of elimination. It meant repeating the experiment over and over again with different chunks of naked DNA
from the tumour cells. But the three teams racing against each other got there within a year, publishing their results in the summer of 1982. They discovered that the oncogene in the human tumour
DNA was one named ‘Ras’. Mirroring the story of the oncogene Src discovered by Varmus and Bishop, Ras turned out to be homologous (that is, very similar,