Free p53 by Sue Armstrong

don’t believe it! You didn’t do anything, and you got a PhD for
that
?” I said, “Listen! You try doing that work when you have to make all your own enzymes . . . There weren’t any kits in those days, you know . . . Everything you take
for granted now was just not there, so it took a long, long time – and it was tricky.”’
    Oren, Levine and Jenkins had, in fact, been beaten to the finishing tape in the highly competitive race to clone p53 by a Russian scientist, Peter Chumakov, working at the Institute of Molecular
Biology in Moscow. But Chumakov had published his results – in December 1982 – in
Proceedings of the Academy of Sciences of the USSR
, a Russian-language journal with limited
readership in the West, and for some time his triumph went unnoticed beyond the Soviet Union. Back in 1979 Chumakov had just completed his doctoral thesis on SV40 and had been looking for a project
that would reveal how large T antigen caused cancer when he heard of the discovery of p53. Excited by the idea that p53 might be the key to the transformation process, he decided to clone the gene
to provide material for further studies.
    But Chumakov faced even greater challenges than his Western competitors. His lab in Moscow had shortages of some of the most basic equipment, such as test tubes and pipettes, which he cleaned
and re-used over and over again. He also had to send off to a scientist in Texas, Elizabeth Gurney, for a sample of the special antibody to p53 she had made and which he realised was vital to his
cloning endeavour. He made his request without much hope of receiving the sophisticated tool. ‘I thought that even if Elizabeth decided to send the sample, a package containing a suspicious
test tube would be stopped either on the USSR border, or during postal censorship that occurred regularly with mail coming from the West,’ he told me. But he was lucky. Visiting a colleague
in a neighbouring lab one day, he noticed a small, foreign-looking package lying on a desk and he turned it over in casual curiosity. To his surprise and delight he found it was addressed to
himself and contained a small phial of the antibody together with a letter from Gurney wishing him success.
    His unexpected good fortune boosted Chumakov’s morale enormously and he was determined to complete his task – especially as he now realised, from his new contacts with the outside
world, that he was not the only one trying to clone this important gene. That he was the first to succeed was finally recognised when his paper came out in English and he began to be invited to
international p53 meetings. ‘There was a wonderful atmosphere of enthusiasm and hope in the lab, and we really felt lucky about being attached to those exciting discoveries in life
sciences,’ he commented.
    For all the research teams involved, the next step after producing a clone of p53 was to determine the sequence of the gene – the words spelled out by its base pairs, A and T, G and C,
that dictate the amino acid composition of its protein. ‘Sequencing was not very difficult, even in those days,’ commented Oren. ‘It was much easier to do than cloning. But it was
all manual: you had to prepare your DNA and all kinds of reagents and run gels and do everything by hand. And you had to read it and interpret it yourself. There were many errors; the method was
not precise enough, but it was not a technical challenge. And by the time I got to it there was already a technician who was doing it routinely.’
    With the information provided by sequencing and a potentially endless supply of clones – some of the whole gene, others of important segments of the gene – researchers were now ready
to start investigating how p53 functions within cells.

CHAPTER SIX
A Case of Mistaken Identity
    In which we: a) discover that we humans also have would-be oncogenes in all our cells; b) learn that what turns oncogenes nasty is mutation; and c) hear that an oncogene