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THREE years after Stanley Prusiner won a Nobel prize for his prion theory,
researchers in California have finally done the crucial experiment that shows he
was right.

It was Prusiner, a biochemist at the University of California, San Francisco
(UCSF), who suggested that the infectious agents behind BSE and related diseases
were completely different from anything discovered before. Instead of viruses or
bacteria being to blame, he said, a protein twisted into an abnormal shape was
triggering the same shape change in its healthy counterpart. In this way, the
abnormal protein, or prion, could 鈥渞eplicate鈥� and the disease spread.

But final proof of Prusiner鈥檚 theory has been elusive because the key
experiment鈥攊njecting pure prions into an animal to see if they can convert
normal proteins into prions and trigger disease鈥攈as not been successful.
Synthetic versions of prion proteins are ineffective and natural prions, while
infectious, cannot answer the question. 鈥淭here always remained the possibility
that other molecules introduced at the same time contributed to the infection,鈥�
says Jonathan Weissman, also at UCSF. Indeed, other researchers have suggested
that viruses hidden in the tangled masses of protein are the true agents of
infection.

So Weissman looked at Sup35, a yeast protein believed to be capable of
prion-like replication. His team purified Sup35 from genetically engineered
bacteria and treated it to induce the abnormal shape change. A sizeable dose of
this putative prion was then given to yeast cells.

These prions triggered conversion of Sup35 in more than 1 per cent of the
cells they invaded, an impressive increase over the spontaneous rate of prion
conversion of one cell in a million. The work provides 鈥渢he finishing touches鈥�
to the protein-only hypothesis, says Mick Tuite at the University of Kent at
Canterbury.

But Laura Manuelidis of Yale University, a leading proponent of the virus
theory, points out that while Weissman鈥檚 prions convert proteins in a cell and
its descendants, they do not spread from cell to adjacent cell. 鈥淚n medicine,
that is the definition of infection,鈥� she says. 鈥淭his is a wonderful story for
yeast, but I鈥檓 not convinced it explains any human or cow disease.鈥�